Journal Description
International Journal of Molecular Sciences
International Journal of Molecular Sciences
is an international, peer-reviewed, open access journal providing an advanced forum for biochemistry, molecular and cell biology, molecular biophysics, molecular medicine, and all aspects of molecular research in chemistry, and is published semimonthly online by MDPI. The Australian Society of Plant Scientists (ASPS), Epigenetics Society, European Calcium Society (ECS), European Chitin Society (EUCHIS), Spanish Society for Cell Biology (SEBC) and others are affiliated with IJMS and their members receive a discount on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, MEDLINE, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q1 (Biochemistry & Molecular Biology) / CiteScore - Q1 (Inorganic Chemistry)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 16.3 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Testimonials: See what our editors and authors say about the IJMS.
- Companion journals for IJMS include: Biophysica, Obesities, Stresses and Lymphatics.
Impact Factor:
5.6 (2022);
5-Year Impact Factor:
6.2 (2022)
Latest Articles
Recent Advancements in Bone Tissue Engineering: Integrating Smart Scaffold Technologies and Bio-Responsive Systems for Enhanced Regeneration
Int. J. Mol. Sci. 2024, 25(11), 6012; https://doi.org/10.3390/ijms25116012 (registering DOI) - 30 May 2024
Abstract
In exploring the challenges of bone repair and regeneration, this review evaluates the potential of bone tissue engineering (BTE) as a viable alternative to traditional methods, such as autografts and allografts. Key developments in biomaterials and scaffold fabrication techniques, such as additive manufacturing
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In exploring the challenges of bone repair and regeneration, this review evaluates the potential of bone tissue engineering (BTE) as a viable alternative to traditional methods, such as autografts and allografts. Key developments in biomaterials and scaffold fabrication techniques, such as additive manufacturing and cell and bioactive molecule-laden scaffolds, are discussed, along with the integration of bio-responsive scaffolds, which can respond to physical and chemical stimuli. These advancements collectively aim to mimic the natural microenvironment of bone, thereby enhancing osteogenesis and facilitating the formation of new tissue. Through a comprehensive combination of in vitro and in vivo studies, we scrutinize the biocompatibility, osteoinductivity, and osteoconductivity of these engineered scaffolds, as well as their interactions with critical cellular players in bone healing processes. Findings from scaffold fabrication techniques and bio-responsive scaffolds indicate that incorporating nanostructured materials and bioactive compounds is particularly effective in promoting the recruitment and differentiation of osteoprogenitor cells. The therapeutic potential of these advanced biomaterials in clinical settings is widely recognized and the paper advocates continued research into multi-responsive scaffold systems.
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(This article belongs to the Section Materials Science)
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Novel Allelic Gene Variations in CmCLAVATA3 (CmCLV3) Were Identified in a Genetic Population of Melon (Cucumis melo L.)
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Hangyu Wu, Yue Jia, Xinxiu Chen, Naiyu Jiang, Zhonghua Zhang and Sen Chai
Int. J. Mol. Sci. 2024, 25(11), 6011; https://doi.org/10.3390/ijms25116011 (registering DOI) - 30 May 2024
Abstract
Carpel number (CN) is an important trait affecting the fruit size and shape of melon, which plays a crucial role in determining the overall appearance and market value. A unique non-synonymous single nucleotide polymorphism (SNP) in CmCLAVATA3 (CmCLV3) is responsible for
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Carpel number (CN) is an important trait affecting the fruit size and shape of melon, which plays a crucial role in determining the overall appearance and market value. A unique non-synonymous single nucleotide polymorphism (SNP) in CmCLAVATA3 (CmCLV3) is responsible for the variation of CN in C. melo ssp. agrestis (hereafter agrestis), but it has been unclear in C. melo ssp. melo (hereafter melo). In this study, one major locus controlling the polymorphism of 5-CN (multi-CN) and 3-CN (normal-CN) in melo was identified using bulked segregant analysis (BSA-seq). This locus was then fine-mapped to an interval of 1.8 Mb on chromosome 12 using a segregating population containing 1451 progeny. CmCLV3 is still present in the candidate region. A new allele of CmCLV3, which contains five other nucleotide polymorphisms, including a non-synonymous SNP in coding sequence (CDS), except the SNP reported in agrestis, was identified in melo. A cis-trans test confirmed that the candidate gene, CmCLV3, contributes to the variation of CNs in melo. The qRT-PCR results indicate that there is no significant difference in the expression level of CmCLV3 in the apical stem between the multi-CN plants and the normal-CN plants. Overall, this study provides a genetic resource for melon fruit development research and molecular breeding. Additionally, it suggests that melo has undergone similar genetic selection but evolved into an independent allele.
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(This article belongs to the Special Issue Vegetable Genetics and Genomics 2.0)
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Open AccessCommunication
In Silico Assessment of Chemical Disinfectants on Surface Proteins Unveiled Dissimilarity in Antiviral Efficacy and Suitability towards Pathogenic Viruses
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Diaiti Zure, Meng-Hau Sung, Abdul Rahim and Hsion-Wen Kuo
Int. J. Mol. Sci. 2024, 25(11), 6009; https://doi.org/10.3390/ijms25116009 (registering DOI) - 30 May 2024
Abstract
Viral pathogens pose a substantial threat to public health and necessitate the development of effective remediation and antiviral strategies. This short communication aimed to investigate the antiviral efficacy of disinfectants on the surface proteins of human pathogenic viruses. Using in silico modeling, the
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Viral pathogens pose a substantial threat to public health and necessitate the development of effective remediation and antiviral strategies. This short communication aimed to investigate the antiviral efficacy of disinfectants on the surface proteins of human pathogenic viruses. Using in silico modeling, the ligand-binding energies (LBEs) of selected disinfectants were predicted and combined with their environmental impacts and costs through an eco-pharmaco-economic analysis (EPEA). The results revealed that the binding affinities of chemical disinfectants to viral proteins varied significantly (p < 0.005). Rutin demonstrated promising broad-spectrum antiviral efficacy with an LBE of −8.49 ± 0.92 kcal/mol across all tested proteins. Additionally, rutin showed a superior eco-pharmaco-economic profile compared to the other chemicals, effectively balancing high antiviral effectiveness, moderate environmental impact, and affordability. These findings highlight rutin as a key phytochemical for use in remediating viral contaminants.
Full article
(This article belongs to the Special Issue Molecular Advance in Cheminformatics and Nanoinformatics: Pioneering Solutions for Modern Challenges)
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Open AccessArticle
Nonclinical Evaluation of Single-Mutant E. coli Asparaginases Obtained by Double-Mutant Deconvolution: Improving Toxicological, Immune and Inflammatory Responses
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Grace Ruiz-Lara, Tales A. Costa-Silva, Jorge Javier Muso-Cachumba, Johanna Cevallos Espinel, Marina Gabriel Fontes, Mitla Garcia-Maya, Khondaker Miraz Rahman, Carlota de Oliveira Rangel-Yagui and Gisele Monteiro
Int. J. Mol. Sci. 2024, 25(11), 6008; https://doi.org/10.3390/ijms25116008 (registering DOI) - 30 May 2024
Abstract
Acute lymphoblastic leukaemia is currently treated with bacterial L-asparaginase; however, its side effects raise the need for the development of improved and efficient novel enzymes. Previously, we obtained low anti-asparaginase antibody production and high serum enzyme half-life in mice treated with the P40S/S206C
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Acute lymphoblastic leukaemia is currently treated with bacterial L-asparaginase; however, its side effects raise the need for the development of improved and efficient novel enzymes. Previously, we obtained low anti-asparaginase antibody production and high serum enzyme half-life in mice treated with the P40S/S206C mutant; however, its specific activity was significantly reduced. Thus, our aim was to test single mutants, S206C and P40S, through in vitro and in vivo assays. Our results showed that the drop in specific activity was caused by P40S substitution. In addition, our single mutants were highly stable in biological environment simulation, unlike the double-mutant P40S/S206C. The in vitro cell viability assay demonstrated that mutant enzymes have a higher cytotoxic effect than WT on T-cell-derived ALL and on some solid cancer cell lines. The in vivo assays were performed in mice to identify toxicological effects, to evoke immunological responses and to study the enzymes’ pharmacokinetics. From these tests, none of the enzymes was toxic; however, S206C elicited lower physiological changes and immune/allergenic responses. In relation to the pharmacokinetic profile, S206C exhibited twofold higher activity than WT and P40S two hours after injection. In conclusion, we present bioengineered E. coli asparaginases with high specific enzyme activity and fewer side effects.
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(This article belongs to the Special Issue Acute Leukemia: From Basic Research to Clinical Application)
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Open AccessReview
Current Insights into Sublethal Effects of Pesticides on Insects
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Merle-Theresa Bartling, Annely Brandt, Henner Hollert and Andreas Vilcinskas
Int. J. Mol. Sci. 2024, 25(11), 6007; https://doi.org/10.3390/ijms25116007 (registering DOI) - 30 May 2024
Abstract
The effect of pesticides on insects is often discussed in terms of acute and chronic toxicity, but an important and often overlooked aspect is the impact of sublethal doses on insect physiology and behavior. Pesticides can influence various physiological parameters of insects, including
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The effect of pesticides on insects is often discussed in terms of acute and chronic toxicity, but an important and often overlooked aspect is the impact of sublethal doses on insect physiology and behavior. Pesticides can influence various physiological parameters of insects, including the innate immune system, development, and reproduction, through a combination of direct effects on specific exposed tissues and the modification of behaviors that contribute to health and reproductive success. Such behaviors include mobility, feeding, oviposition, navigation, and the ability to detect pheromones. Pesticides also have a profound effect on insect learning and memory. The precise effects depend on many different factors, including the insect species, age, sex, caste, physiological condition, as well as the type and concentration of the active ingredients and the exposure route. More studies are needed to assess the effects of different active ingredients (and combinations thereof) on a wider range of species to understand how sublethal doses of pesticides can contribute to insect decline. This review reflects our current knowledge about sublethal effects of pesticides on insects and advancements in the development of innovative methods to detect them.
Full article
(This article belongs to the Special Issue Molecular Ecology, Physiology and Biochemistry of Insects, 4th Edition)
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Open AccessArticle
Probing the Conformational Restraints of DNA Damage Recognition with β-L-Nucleotides
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Anna V. Yudkina, Daria V. Kim, Timofey D. Zharkov, Dmitry O. Zharkov and Anton V. Endutkin
Int. J. Mol. Sci. 2024, 25(11), 6006; https://doi.org/10.3390/ijms25116006 (registering DOI) - 30 May 2024
Abstract
The DNA building blocks 2′-deoxynucleotides are enantiomeric, with their natural β-D-configuration dictated by the sugar moiety. Their synthetic β-L-enantiomers (βLdNs) can be used to obtain L-DNA, which, when fully substituted, is resistant to nucleases and is finding use in many biosensing and nanotechnology
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The DNA building blocks 2′-deoxynucleotides are enantiomeric, with their natural β-D-configuration dictated by the sugar moiety. Their synthetic β-L-enantiomers (βLdNs) can be used to obtain L-DNA, which, when fully substituted, is resistant to nucleases and is finding use in many biosensing and nanotechnology applications. However, much less is known about the enzymatic recognition and processing of individual βLdNs embedded in D-DNA. Here, we address the template properties of βLdNs for several DNA polymerases and the ability of base excision repair enzymes to remove these modifications from DNA. The Klenow fragment was fully blocked by βLdNs, whereas DNA polymerase κ bypassed them in an error-free manner. Phage RB69 DNA polymerase and DNA polymerase β treated βLdNs as non-instructive but the latter enzyme shifted towards error-free incorporation on a gapped DNA substrate. DNA glycosylases and AP endonucleases did not process βLdNs. DNA glycosylases sensitive to the base opposite their cognate lesions also did not recognize βLdNs as a correct pairing partner. Nevertheless, when placed in a reporter plasmid, pyrimidine βLdNs were resistant to repair in human cells, whereas purine βLdNs appear to be partly repaired. Overall, βLdNs are unique modifications that are mostly non-instructive but have dual non-instructive/instructive properties in special cases.
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(This article belongs to the Section Biochemistry)
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Single-Base Gene Variants in MIR-146A and SCN1A Genes Related to the Epileptogenic Process in Drug-Responsive and Drug-Resistant Temporal Lobe Epilepsy—A Preliminary Study in a Brazilian Cohort Sample
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Renata Parissi Buainain, André Rodrigues Sodré, Jéssica Silva dos Santos, Karen Antonia Girotto Takazaki, Luciano de Souza Queiroz, Carlos Tadeu Parisi de Oliveira, Paulo Henrique Pires de Aguiar, Fernando Augusto Lima Marson and Manoela Marques Ortega
Int. J. Mol. Sci. 2024, 25(11), 6005; https://doi.org/10.3390/ijms25116005 (registering DOI) - 30 May 2024
Abstract
The drug-resistant temporal lobe epilepsy (TLE) has recently been associated with single nucleotide variants (SNVs) in microRNA(miR)-146a (MIR-146A) (rs2910164) and Sodium Voltage-Gated Channel Alpha Subunit 1 (SCN1A) (rs2298771 and rs3812718) genes. Moreover, no studies have shown an association between
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The drug-resistant temporal lobe epilepsy (TLE) has recently been associated with single nucleotide variants (SNVs) in microRNA(miR)-146a (MIR-146A) (rs2910164) and Sodium Voltage-Gated Channel Alpha Subunit 1 (SCN1A) (rs2298771 and rs3812718) genes. Moreover, no studies have shown an association between these SNVs and susceptibility to drug-resistant and drug-responsive TLE in Brazil. Thus, deoxyribonucleic acid (DNA) samples from 120 patients with TLE (55 drug-responsive and 65 drug-resistant) were evaluated by real-time polymerase chain reaction (RT-PCR). A total of 1171 healthy blood donor individuals from the Online Archive of Brazilian Mutations (ABraOM, from Portuguese Arquivo Brasileiro On-line de Mutações), a repository containing genomic variants of the Brazilian population, were added as a control population for the studied SNVs. MIR-146A and SCN1A relative expression was performed by quantitative RT-PCR (qRT-PCR). The statistical analysis protocol was performed using an alpha error of 0.05. TLE patient samples and ABraOM control samples were in Hardy–Weinberg equilibrium for all studied SNVs. For rs2910164, the frequencies of the homozygous genotype (CC) (15.00% vs. 9.65%) and C allele (37.80% vs. 29.97%) were superior in patients with TLE compared to controls with a higher risk for TLE disease [odds ratio (OR) = 1.89 (95% confidence interval (95%CI) = 1.06–3.37); OR = 1.38 (95%CI = 1.04–1.82), respectively]. Drug-responsive patients also presented higher frequencies of the CC genotype [21.81% vs. 9.65%; OR = 2.58 (95%CI = 1.25–5.30)] and C allele [39.09% vs. 29.97%; OR = 1.50 (95%CI = 1.01–2.22)] compared to controls. For rs2298771, the frequency of the heterozygous genotype (AG) (51.67% vs. 40.40%) was superior in patients with TLE compared to controls with a higher risk for TLE disease [OR = 2.42 (95%CI = 1.08–5.41)]. Drug-resistant patients presented a higher AG frequency [56.92% vs. 40.40%; OR = 3.36 (95%CI = 1.04–17.30)] compared to the control group. For rs3812718, the prevalence of genotypes and alleles were similar in both studied groups. The MIR-146A relative expression level was lower in drug-resistant compared to drug-responsive patients for GC (1.6 vs. 0.1, p-value = 0.049) and CC (1.8 vs. 0.6, p-value = 0.039). Also, the SCN1A relative expression levels in samples from TLE patients were significantly higher in AG [2.09 vs. 1.10, p-value = 0.038] and GG (3.19 vs. 1.10, p-value < 0.001) compared to the AA genotype. In conclusion, the rs2910164-CC and rs2298771-AG genotypes are exerting significant risk influence, respectively, on responsive disease and resistant disease, probably due to an upregulated nuclear factor kappa B (NF-kB) and SCN1A loss of function.
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(This article belongs to the Special Issue Role of Mutations and Polymorphisms in Various Diseases)
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Fibroblast Diversity and Epigenetic Regulation in Cardiac Fibrosis
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Laura Pilar Aguado-Alvaro, Nerea Garitano and Beatriz Pelacho
Int. J. Mol. Sci. 2024, 25(11), 6004; https://doi.org/10.3390/ijms25116004 (registering DOI) - 30 May 2024
Abstract
Cardiac fibrosis, a process characterized by excessive extracellular matrix (ECM) deposition, is a common pathological consequence of many cardiovascular diseases (CVDs) normally resulting in organ failure and death. Cardiac fibroblasts (CFs) play an essential role in deleterious cardiac remodeling and dysfunction. In response
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Cardiac fibrosis, a process characterized by excessive extracellular matrix (ECM) deposition, is a common pathological consequence of many cardiovascular diseases (CVDs) normally resulting in organ failure and death. Cardiac fibroblasts (CFs) play an essential role in deleterious cardiac remodeling and dysfunction. In response to injury, quiescent CFs become activated and adopt a collagen-secreting phenotype highly contributing to cardiac fibrosis. In recent years, studies have been focused on the exploration of molecular and cellular mechanisms implicated in the activation process of CFs, which allow the development of novel therapeutic approaches for the treatment of cardiac fibrosis. Transcriptomic analyses using single-cell RNA sequencing (RNA-seq) have helped to elucidate the high cellular diversity and complex intercellular communication networks that CFs establish in the mammalian heart. Furthermore, a significant body of work supports the critical role of epigenetic regulation on the expression of genes involved in the pathogenesis of cardiac fibrosis. The study of epigenetic mechanisms, including DNA methylation, histone modification, and chromatin remodeling, has provided more insights into CF activation and fibrotic processes. Targeting epigenetic regulators, especially DNA methyltransferases (DNMT), histone acetylases (HAT), or histone deacetylases (HDAC), has emerged as a promising approach for the development of novel anti-fibrotic therapies. This review focuses on recent transcriptomic advances regarding CF diversity and molecular and epigenetic mechanisms that modulate the activation process of CFs and their possible clinical applications for the treatment of cardiac fibrosis.
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(This article belongs to the Special Issue Current Research for Heart Disease Biology and Therapeutics 2.0)
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CAFs-Associated Genes (CAFGs) in Pancreatic Ductal Adenocarcinoma (PDAC) and Novel Therapeutic Strategy
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Keishi Yamashita and Yusuke Kumamoto
Int. J. Mol. Sci. 2024, 25(11), 6003; https://doi.org/10.3390/ijms25116003 (registering DOI) - 30 May 2024
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive cancer with striking fibrosis, and its mortality rate is ranked second across human cancers. Cancer-associated fibroblasts (CAFs) play a critical role in PDAC progression, and we reviewed the molecular understanding of PDAC CAFs and novel
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Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive cancer with striking fibrosis, and its mortality rate is ranked second across human cancers. Cancer-associated fibroblasts (CAFs) play a critical role in PDAC progression, and we reviewed the molecular understanding of PDAC CAFs and novel therapeutic potential at present. CAFs-associated genes (CAFGs) were tentatively classified into three categories by stroma specificity representing stroma/epithelia expression ratios (SE ratios). The recent classification using single cell transcriptome technology clarified that CAFs were composed of myofibroblasts (myCAFs), inflammatory CAFs (iCAFs), and other minor ones (e.g., POSTN-CAFs and antigen presenting CAFs, apCAFs). LRRC15 is a myCAFs marker, and myCAFs depletion by diphtheria toxin induces the rapid accumulation of cytotoxic T lymphocytes (CTLs) and therefore augment PDL1 antibody treatments. This finding proposes that myCAFs may be a critical regulator of tumor immunity in terms of PDAC progression. myCAFs are located in CAFs adjacent to tumor cells, while iCAFs marked by PDPN and/or COL14A1 are distant from tumor cells, where hypoxic and acidic environments being located in iCAFs putatively due to poor blood supply is consistent with HIF1A and GPR68 expressions. iCAFs may be shared with SASP (secretion-associated phenotypes) in senescent CAFs. myCAFs are classically characterized by CAFGs induced by TGFB1, while chemoresistant CAFs with SASP may dependent on IL6 expression and accompanied by STAT3 activation. Recently, it was found that the unique metabolism of CAFs can be targeted to prevent PDAC progression, where PDAC cells utilize glucose, whereas CAFs in turn utilize lactate, which may be epigenetically regulated, mediated by its target genes including CXCR4. In summary, CAFs have unique molecular characteristics, which have been rigorously clarified as novel therapeutic targets of PDAC progression.
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(This article belongs to the Special Issue Pancreatic Disease: From Molecular Basis to Novel Therapies)
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The Diagnostic and Prognostic Potentials of Non-Coding RNA in Cholangiocarcinoma
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Rita Andrade, Ilda Patrícia Ribeiro, Isabel Marques Carreira and José Guilherme Tralhão
Int. J. Mol. Sci. 2024, 25(11), 6002; https://doi.org/10.3390/ijms25116002 (registering DOI) - 30 May 2024
Abstract
Cholangiocarcinoma (CCA) is a rare biliary tract tumor with high malignancy. CCA is the second most common primary hepatobiliary cancer after hepatocarcinoma. Despite its rarity, the incidence of CCA is steadily increasing globally. Most patients with CCA are asymptomatic in the early stages,
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Cholangiocarcinoma (CCA) is a rare biliary tract tumor with high malignancy. CCA is the second most common primary hepatobiliary cancer after hepatocarcinoma. Despite its rarity, the incidence of CCA is steadily increasing globally. Most patients with CCA are asymptomatic in the early stages, resulting in a late-stage diagnosis and poor prognosis. Finding reliable biomarkers is essential to improve CCA’s early diagnosis and survival rate. Non-coding RNAs (ncRNAs) are non-protein coding RNAs produced by genomic transcription. This includes microRNAs, long non-coding RNAs, and circular RNAs. ncRNAs have multiple functions in regulating gene expression and are crucial for maintaining normal cell function and developing diseases. Many studies have shown that aberrantly expressed ncRNAs can regulate the occurrence and development of CCA. ncRNAs can be easily extracted and detected through tumor tissue and liquid biopsies, representing a potential tool for diagnosing and prognosis CCA. This review will provide a detailed update on the diagnostic and prognostic potentials of lncRNAs and cirRNAs as biomarkers in CCA.
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(This article belongs to the Special Issue Pathways in Development and Disease: The Role of RNA Regulation in Biological and Pathological Events)
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Open AccessArticle
Unique Self-Phosphorylating Polybenzimidazole of the 6F Family for HT-PEM Fuel Cell Application
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Igor I. Ponomarev, Yulia A. Volkova, Kirill M. Skupov, Elizaveta S. Vtyurina, Ivan I. Ponomarev, Mikhail M. Ilyin, Roman Y. Nikiforov, Alexander Y. Alentiev, Olga M. Zhigalina, Dmitry N. Khmelenin, Tatyana V. Strelkova and Alexander D. Modestov
Int. J. Mol. Sci. 2024, 25(11), 6001; https://doi.org/10.3390/ijms25116001 (registering DOI) - 30 May 2024
Abstract
High-temperature polymer-electrolyte membrane fuel cells (HT-PEMFCs) are a very important type of fuel cells since they operate at 150–200 °C, making it possible to use hydrogen contaminated with CO. However, the need to improve the stability and other properties of gas-diffusion electrodes still
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High-temperature polymer-electrolyte membrane fuel cells (HT-PEMFCs) are a very important type of fuel cells since they operate at 150–200 °C, making it possible to use hydrogen contaminated with CO. However, the need to improve the stability and other properties of gas-diffusion electrodes still impedes their distribution. Self-supporting anodes based on carbon nanofibers (CNF) are prepared using the electrospinning method from a polyacrylonitrile solution containing zirconium salt, followed by pyrolysis. After the deposition of Pt nanoparticles on the CNF surface, the composite anodes are obtained. A new self-phosphorylating polybenzimidazole of the 6F family is applied to the Pt/CNF surface to improve the triple-phase boundary, gas transport, and proton conductivity of the anode. This polymer coating ensures a continuous interface between the anode and proton-conducting membrane. The polymer is investigated using CO2 adsorption, TGA, DTA, FTIR, GPC, and gas permeability measurements. The anodes are studied using SEM, HAADF STEM, and CV. The operation of the membrane–electrode assembly in the H2/air HT-PEMFC shows that the application of the new PBI of the 6F family with good gas permeability as a coating for the CNF anodes results in an enhancement of HT-PEMFC performance, reaching 500 mW/cm2 at 1.3 A/cm2 (at 180 °C), compared with the previously studied PBI-O-PhT-P polymer.
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(This article belongs to the Section Physical Chemistry and Chemical Physics)
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Exploring the Neuroprotective Potential of N-Methylpyridinium against LPS-Induced Neuroinflammation: Insights from Molecular Mechanisms
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Laura Giannotti, Benedetta Di Chiara Stanca, Francesco Spedicato, Eleonora Stanca, Fabrizio Damiano, Stefano Quarta, Marika Massaro and Luisa Siculella
Int. J. Mol. Sci. 2024, 25(11), 6000; https://doi.org/10.3390/ijms25116000 (registering DOI) - 30 May 2024
Abstract
N-methylpyridinium (NMP) is produced through the pyrolysis of trigonelline during the coffee bean roasting process. Preliminary studies suggest that NMP may have health benefits, thanks to its antioxidant properties. Based on this background, the aim of this study was to evaluate whether NMP
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N-methylpyridinium (NMP) is produced through the pyrolysis of trigonelline during the coffee bean roasting process. Preliminary studies suggest that NMP may have health benefits, thanks to its antioxidant properties. Based on this background, the aim of this study was to evaluate whether NMP could have a protective effect against LPS-induced neuroinflammation in human glioblastoma cells (U87MG). With this aim, U87MG cells were pre-treated with NMP (0.5 μM) for 1 h and then exposed to LPS (1 μg/mL) for 24 h. Our findings show that NMP attenuates LPS-induced neuroinflammation by reducing the expression of pro-inflammatory cytokines, such as IL-1β, TNF-α and IL-6, through the inhibition of the NF-κB signaling pathway, which is critical in regulating inflammatory responses. NMP is able to suppress the activation of the NF-κB signaling pathway, suggesting its potential in preventing neuroinflammatory conditions. These outcomes support the notion that regular consumption of NMP, possibly through coffee consumption, may offer protection against neuroinflammatory states implicated in neurological disorders.
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(This article belongs to the Special Issue Neuroinflammatory Mediator in Neurodegenerative Disease)
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Open AccessArticle
Antibacterial and Antioxidant Activity of Synthetic Polyoxygenated Flavonoids
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Mauricio Enrique Osorio-Olivares, Yesseny Vásquez-Martínez, Katy Díaz, Javiera Canelo, Lautaro Taborga and Luis Espinoza-Catalán
Int. J. Mol. Sci. 2024, 25(11), 5999; https://doi.org/10.3390/ijms25115999 (registering DOI) - 30 May 2024
Abstract
Flavonoids are an abundant class of naturally occurring compounds with broad biological activities, but their limited abundance in nature restricts their use in medicines and food additives. Here we present the synthesis and determination of the antibacterial and antioxidant activities of twenty-two structurally
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Flavonoids are an abundant class of naturally occurring compounds with broad biological activities, but their limited abundance in nature restricts their use in medicines and food additives. Here we present the synthesis and determination of the antibacterial and antioxidant activities of twenty-two structurally related flavonoids (five of which are new) by scientifically validated methods. Flavanones (FV1–FV11) had low inhibitory activity against the bacterial growth of MRSA 97-7. However, FV2 (C5,7,3′,4′ = OH) and FV6 (C5,7 = OH; C4′ = SCH3) had excellent bacterial growth inhibitory activity against Gram-negative E. coli (MIC = 25 µg/mL for both), while Chloramphenicol (MIC = 25 µg/mL) and FV1 (C5,7,3′ = OCH3; 4′ = OH) showed inhibitory activity against Gram-positive L. monocytogenes (MIC = 25 µg/mL). From the flavone series (FO1–FO11), FO2 (C5,7,3′,4′ = OH), FO3 (C5,7,4′ = OH; 3′ = OCH3), and FO5 (C5,7,4′ = OH) showed good inhibitory activity against Gram-positive MRSA 97-7 (MIC = 50, 12, and 50 µg/mL, respectively), with FO3 being more active than the positive control Vancomycin (MIC = 25 µg/mL). FO10 (C5,7= OH; 4′ = OCH3) showed high inhibitory activity against E. coli and L. monocytogenes (MIC = 25 and 15 µg/mL, respectively). These data add significantly to our knowledge of the structural requirements to combat these human pathogens. The positions and number of hydroxyl groups were key to the antibacterial and antioxidant activities.
Full article
(This article belongs to the Special Issue Antibacterial and Antioxidant Effects of Plant-Sourced Compounds)
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Open AccessArticle
Pygo-F773W Mutation Reveals Novel Functions beyond Wnt Signaling in Drosophila
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Youfeng Li, Zhigang Jiang, Yue Xu, Jing Yan, Qiong Wu, Sirui Huang, Lingxiao Wang, Yulian Xie, Xiushan Wu, Yuequn Wang, Yongqing Li, Xiongwei Fan, Fang Li and Wuzhou Yuan
Int. J. Mol. Sci. 2024, 25(11), 5998; https://doi.org/10.3390/ijms25115998 (registering DOI) - 30 May 2024
Abstract
Pygopus (Pygo) has been identified as a specific nuclear co-activator of the canonical Wingless (Wg)/Wnt signaling pathway in Drosophila melanogaster. Pygo proteins consist of two conserved domains: an N-terminal homologous domain (NHD) and a C-terminal plant homologous domain (PHD). The PHD’s ability
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Pygopus (Pygo) has been identified as a specific nuclear co-activator of the canonical Wingless (Wg)/Wnt signaling pathway in Drosophila melanogaster. Pygo proteins consist of two conserved domains: an N-terminal homologous domain (NHD) and a C-terminal plant homologous domain (PHD). The PHD’s ability to bind to di- and trimethylated lysine 4 of histone H3 (H3K4me2/3) appears to be independent of Wnt signaling. There is ongoing debate regarding the significance of Pygo’s histone-binding capacity. Drosophila Pygo orthologs have a tryptophan (W) > phenylalanine (F) substitution in their histone pocket-divider compared to vertebrates, leading to reduced histone affinity. In this research, we utilized CRISPR/Cas9 technology to introduce the Pygo-F773W point mutation in Drosophila, successfully establishing a viable homozygous Pygo mutant line for the first time. Adult mutant flies displayed noticeable abnormalities in reproduction, locomotion, heart function, and lifespan. RNA-seq and cluster analysis indicated that the mutation primarily affected pathways related to immunity, metabolism, and posttranslational modification in adult flies rather than the Wnt signaling pathway. Additionally, a reduction in H3K9 acetylation levels during the embryonic stage was observed in the mutant strains. These findings support the notion that Pygo plays a wider role in chromatin remodeling, with its involvement in Wnt signaling representing only a specific aspect of its chromatin-related functions.
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(This article belongs to the Special Issue Molecular Genetics of Drosophila Development)
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Open AccessArticle
The Improved Antigen Uptake and Presentation of Dendritic Cells Using Cell-Penetrating D-octaarginine-Linked PNVA-co-AA as a Novel Dendritic Cell-Based Vaccine
by
Yuri Fujioka, Hideto Ueki, Ruhan A, Akari Sasajima, Takumi Tomono, Masami Ukawa, Haruya Yagi, Shinji Sakuma, Koichi Kitagawa and Toshiro Shirakawa
Int. J. Mol. Sci. 2024, 25(11), 5997; https://doi.org/10.3390/ijms25115997 (registering DOI) - 30 May 2024
Abstract
Cancer immunotherapy using antigen-pulsed dendritic cells can induce strong cellular immune responses by priming cytotoxic T lymphocytes. In this study, we pulsed tumor cell lysates with VP-R8, a cell-penetrating D-octaarginine-linked co-polymer of N-vinylacetamide and acrylic acid (PNVA-co-AA), into the DC2.4 murine dendritic cell
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Cancer immunotherapy using antigen-pulsed dendritic cells can induce strong cellular immune responses by priming cytotoxic T lymphocytes. In this study, we pulsed tumor cell lysates with VP-R8, a cell-penetrating D-octaarginine-linked co-polymer of N-vinylacetamide and acrylic acid (PNVA-co-AA), into the DC2.4 murine dendritic cell line to improve antigen uptake and then determined the anti-tumor effect in tumor-bearing mice. DC2.4 cells were pulsed with the cell lysate of EL4, a murine lymphoma cell line, and VP-R8 to generate the DC2.4 vaccine. For the in vivo study, DC2.4 cells pulsed with EL4 lysate and VP-R8 were subcutaneously injected into the inguinal lymph node to investigate the anti-tumor effect against EL4 and EL4-specific T cell immune responses. VP-R8 significantly improved antigen uptake into DC2.4 compared to conventional keyhole limpet hemocyanin (p < 0.05). The expression of MHC class I, MHC class II, and CD86 in DC2.4 cells significantly increased after pulsing tumor lysates with VP-R8 compared to other treatments (p < 0.05). The intra-lymph node injection of DC2.4 pulsed with both VP-R8 and EL4 lysate significantly decreased tumor growth compared to DC2.4 pulsed with KLH and lysates (p < 0.05) and induced tumor-infiltrating CD8T cells. The DC2.4 vaccine also remarkably increased the population of IFN-gamma-producing T cells and CTL activity against EL4 cells. In conclusion, we demonstrated that VP-R8 markedly enhances the efficiency of dendritic cell-based vaccines in priming robust anti-tumor immunity, suggesting its potential as a beneficial additive for dendritic cell-based immunotherapy.
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(This article belongs to the Special Issue Dendritic Cell and Cancer Therapy 2.0)
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Open AccessReview
Infrared Spectroscopy in Gynecological Oncology: A Comprehensive Review of Diagnostic Potentials and Challenges
by
Charlotte Delrue, Sander De Bruyne, Matthijs Oyaert, Joris R. Delanghe, Rafael Noal Moresco, Reinhart Speeckaert and Marijn M. Speeckaert
Int. J. Mol. Sci. 2024, 25(11), 5996; https://doi.org/10.3390/ijms25115996 (registering DOI) - 30 May 2024
Abstract
The early detection of gynecological cancers, which is critical for improving patient survival rates, is challenging because of the vague early symptoms and the diagnostic limitations of current approaches. This comprehensive review delves into the game-changing potential of infrared (IR) spectroscopy, a noninvasive
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The early detection of gynecological cancers, which is critical for improving patient survival rates, is challenging because of the vague early symptoms and the diagnostic limitations of current approaches. This comprehensive review delves into the game-changing potential of infrared (IR) spectroscopy, a noninvasive technology used to transform the landscape of cancer diagnosis in gynecology. By collecting the distinctive vibrational frequencies of chemical bonds inside tissue samples, Fourier-transform infrared (FTIR) spectroscopy provides a ‘molecular fingerprint’ that outperforms existing diagnostic approaches. We highlight significant advances in this field, particularly the identification of discrete biomarker bands in the mid- and near-IR spectra. Proteins, lipids, carbohydrates, and nucleic acids exhibited different absorption patterns. These spectral signatures not only serve to distinguish between malignant and benign diseases, but also provide additional information regarding the cellular changes associated with cancer. To underscore the practical consequences of these findings, we examined studies in which IR spectroscopy demonstrated exceptional diagnostic accuracy. This review supports the use of IR spectroscopy in normal clinical practice, emphasizing its capacity to detect and comprehend the intricate molecular underpinnings of gynecological cancers.
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(This article belongs to the Special Issue Latest Review Papers in Molecular Oncology 2024)
Open AccessReview
Polymorphisms of DNA Repair Genes in Thyroid Cancer
by
Adrianna Gielecińska, Mateusz Kciuk, Damian Kołat, Weronika Kruczkowska and Renata Kontek
Int. J. Mol. Sci. 2024, 25(11), 5995; https://doi.org/10.3390/ijms25115995 (registering DOI) - 30 May 2024
Abstract
The incidence of thyroid cancer, one of the most common forms of endocrine cancer, is increasing rapidly worldwide in developed and developing countries. Various risk factors can increase susceptibility to thyroid cancer, but particular emphasis is put on the role of DNA repair
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The incidence of thyroid cancer, one of the most common forms of endocrine cancer, is increasing rapidly worldwide in developed and developing countries. Various risk factors can increase susceptibility to thyroid cancer, but particular emphasis is put on the role of DNA repair genes, which have a significant impact on genome stability. Polymorphisms of these genes can increase the risk of developing thyroid cancer by affecting their function. In this article, we present a concise review on the most common polymorphisms of selected DNA repair genes that may influence the risk of thyroid cancer. We point out significant differences in the frequency of these polymorphisms between various populations and their potential relationship with susceptibility to the disease. A more complete understanding of these differences may lead to the development of effective prevention strategies and targeted therapies for thyroid cancer. Simultaneously, there is a need for further research on the role of polymorphisms of previously uninvestigated DNA repair genes in the context of thyroid cancer, which may contribute to filling the knowledge gaps on this subject.
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(This article belongs to the Section Molecular Oncology)
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Transcriptome Analysis of Potato Leaves under Oxidative Stress
by
Juping Liu, Xun Tang, Huanhuan Zhang, Meng Wei, Ning Zhang and Huaijun Si
Int. J. Mol. Sci. 2024, 25(11), 5994; https://doi.org/10.3390/ijms25115994 (registering DOI) - 30 May 2024
Abstract
Potato (Solanum tuberosum L.) is a major global food crop, and oxidative stress can significantly impact its growth. Previous studies have shown that its resistance to oxidative stress is mainly related to transcription factors, post-translational modifications, and antioxidant enzymes in vivo, but
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Potato (Solanum tuberosum L.) is a major global food crop, and oxidative stress can significantly impact its growth. Previous studies have shown that its resistance to oxidative stress is mainly related to transcription factors, post-translational modifications, and antioxidant enzymes in vivo, but the specific molecular mechanisms remain unclear. In this study, we analyzed the transcriptome data from potato leaves treated with H2O2 and Methyl viologen (MV), and a control group, for 12 h. We enriched 8334 (CK vs. H2O2) and 4445 (CK vs. MV) differentially expressed genes (DEGs), respectively, and randomly selected 15 DEGs to verify the sequencing data by qRT-PCR. Gene ontology (GO) enrichment analysis showed that the DEGs were mainly concentrated in cellular components and related to molecular function, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that most of the DEGs were related to metabolic pathways, plant hormone signal transduction, MAPK-signaling pathway, and plant–pathogen interactions. In addition, several candidate transcription factors, mainly including MYB, WRKY, and genes associated with Ca2+-mediated signal transduction, were also found to be differentially expressed. Among them, the plant hormone genes Soltu.DM.03G022780 and Soltu.DM.06G019360, the CNGC gene Soltu.DM.06G006320, the MYB transcription factors Soltu.DM.06G004450 and Soltu.DM.09G002130, and the WRKY transcription factor Soltu.DM.06G020440 were noticeably highly expressed, which indicates that these are likely to be the key genes in the regulation of oxidative stress tolerance. Overall, these findings lay the foundation for further studies on the molecular mechanisms of potato leaves in response to oxidative stress.
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(This article belongs to the Special Issue Biotic and Abiotic Stress Effects on Plant Structure and Physiology 2024)
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Effect of the Proximity to the Quintero-Puchuncaví Industrial Zone on Compounds Isolated from Baccharis macraei Hook. & Arn: Their Antioxidant and Cytotoxic Activity
by
Manuel Martínez-Lobos, Estela Tapia-Venegas, Paula Celis-Plá, Joan Villena, Carlos Jara-Gutiérrez, Alexandra Lobos-Pessini, Daniela Rigano, Carmina Sirignano and Alejandro Madrid-Villegas
Int. J. Mol. Sci. 2024, 25(11), 5993; https://doi.org/10.3390/ijms25115993 (registering DOI) - 30 May 2024
Abstract
Baccharis macraei Hook. & Arn (Asteraceae), commonly known as Vautro, is found in the coastal areas of central-southern Chile, including the industrial zone of Quintero-Puchuncaví, known for the contamination of its soils with heavy metals, which together with other factors generate abiotic stress
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Baccharis macraei Hook. & Arn (Asteraceae), commonly known as Vautro, is found in the coastal areas of central-southern Chile, including the industrial zone of Quintero-Puchuncaví, known for the contamination of its soils with heavy metals, which together with other factors generate abiotic stress in plant species, against which they present defensive mechanisms. For this reason, the objective was to evaluate the effect of abiotic stress generated by the proximity of B. macraei to the industrial complex by assessing the physiological and metabolic states reported by the extracts and compounds isolated from the species, as well as the photosynthetic capacity, metal content and production, and antioxidant activity and cytotoxicity against tumorigenic cell lines of the phytoconstituents. To this end, B. macraei was collected at two different distances from the industrial complex, observing that the closer the species is, the greater the concentration of copper in the soil, generating a decrease in the rate of electron transport in situ, but an increase in antioxidant activity with low cytotoxicity. This activity could be due to the presence of flavonoids such as Hispidulin, Cirsimaritina, and Isokaempferida, as well as monoterpenes, oxygenated and non-oxygenated sesquiterpenes identified in this study.
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(This article belongs to the Special Issue Plant-Sourced Functional and Bioactive Compounds—Nature’s Blueprint for Improving Human Well-Being)
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IMPDH Inhibition Decreases TERT Expression and Synergizes the Cytotoxic Effect of Chemotherapeutic Agents in Glioblastoma Cells
by
Xiaoqin Liu, Junying Wang, Laura J. Wu, Britni Trinh and Robert Y. L. Tsai
Int. J. Mol. Sci. 2024, 25(11), 5992; https://doi.org/10.3390/ijms25115992 (registering DOI) - 30 May 2024
Abstract
IMP dehydrogenase (IMPDH) inhibition has emerged as a new target therapy for glioblastoma multiforme (GBM), which remains one of the most refractory tumors to date. TCGA analyses revealed distinct expression profiles of IMPDH isoenzymes in various subtypes of GBM and low-grade glioma (LGG).
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IMP dehydrogenase (IMPDH) inhibition has emerged as a new target therapy for glioblastoma multiforme (GBM), which remains one of the most refractory tumors to date. TCGA analyses revealed distinct expression profiles of IMPDH isoenzymes in various subtypes of GBM and low-grade glioma (LGG). To dissect the mechanism(s) underlying the anti-tumor effect of IMPDH inhibition in adult GBM, we investigated how mycophenolic acid (MPA, an IMPDH inhibitor) treatment affected key oncogenic drivers in glioblastoma cells. Our results showed that MPA decreased the expression of telomerase reverse transcriptase (TERT) in both U87 and U251 cells, and the expression of O6-methylguanine-DNA methyltransferase (MGMT) in U251 cells. In support, MPA treatment reduced the amount of telomere repeats in U87 and U251 cells. TERT downregulation by MPA was associated with a significant decrease in c-Myc (a TERT transcription activator) in U87 but not U251 cells, and a dose-dependent increase in p53 and CCCTC-binding factor (CTCF) (TERT repressors) in both U87 and U251 cells. In U251 cells, MPA displayed strong cytotoxic synergy with BCNU and moderate synergy with irinotecan, oxaliplatin, paclitaxel, or temozolomide (TMZ). In U87 cells, MPA displayed strong cytotoxic synergy with all except TMZ, acting primarily through the apoptotic pathway. Our work expands the mechanistic potential of IMPDH inhibition to TERT/telomere regulation and reveals a synthetic lethality between MPA and anti-GBM drugs.
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(This article belongs to the Section Molecular Biology)
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