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
Aspartate β-Hydroxylase Is Upregulated in Head and Neck Squamous Cell Carcinoma and Regulates Invasiveness in Cancer Cell Models
Int. J. Mol. Sci. 2024, 25(9), 4998; https://doi.org/10.3390/ijms25094998 (registering DOI) - 03 May 2024
Abstract
Aspartate β-hydroxylase (ASPH) is a protein associated with malignancy in a wide range of tumors. We hypothesize that inhibition of ASPH activity could have anti-tumor properties in patients with head and neck cancer. In this study, we screened tumor tissues of 155 head
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Aspartate β-hydroxylase (ASPH) is a protein associated with malignancy in a wide range of tumors. We hypothesize that inhibition of ASPH activity could have anti-tumor properties in patients with head and neck cancer. In this study, we screened tumor tissues of 155 head and neck squamous cell carcinoma (HNSCC) patients for the expression of ASPH using immunohistochemistry. We used an ASPH inhibitor, MO-I-1151, known to inhibit the catalytic activity of ASPH in the endoplasmic reticulum, to show its inhibitory effect on the migration of SCC35 head and neck cancer cells in cell monolayers and in matrix-embedded spheroid co-cultures with primary cancer-associated fibroblast (CAF) CAF 61137 of head and neck origin. We also studied a combined effect of MO-I-1151 and HfFucCS, an inhibitor of invasion-blocking heparan 6-O-endosulfatase activity. We found ASPH was upregulated in HNSCC tumors compared to the adjacent normal tissues. ASPH was uniformly high in expression, irrespective of tumor stage. High expression of ASPH in tumors led us to consider it as a therapeutic target in cell line models. ASPH inhibitor MO-I-1151 had significant effects on reducing migration and invasion of head and neck cancer cells, both in monolayers and matrix-embedded spheroids. The combination of the two enzyme inhibitors showed an additive effect on restricting invasion in the HNSCC cell monolayers and in the CAF-containing co-culture spheroids. We identify ASPH as an abundant protein in HNSCC tumors. Targeting ASPH with inhibitor MO-I-1151 effectively reduces CAF-mediated cellular invasion in cancer cell models. We propose that the additive effect of MO-I-1151 with HfFucCS, an inhibitor of heparan 6-O-endosulfatases, on HNSCC cells could improve interventions and needs to be further explored.
Full article
(This article belongs to the Special Issue Pathogenesis and Treatments of Head and Neck Cancer)
Open AccessReview
An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis
by
Rita Pereira and Rui Bergantim
Int. J. Mol. Sci. 2024, 25(9), 4996; https://doi.org/10.3390/ijms25094996 (registering DOI) - 03 May 2024
Abstract
Multiple myeloma (MM), the second most common hematologic malignancy, remains incurable, and its incidence is rising. Chimeric Antigen Receptor T-cell (CAR-T cell) therapy has emerged as a novel treatment, with the potential to improve the survival and quality of life of patients with
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Multiple myeloma (MM), the second most common hematologic malignancy, remains incurable, and its incidence is rising. Chimeric Antigen Receptor T-cell (CAR-T cell) therapy has emerged as a novel treatment, with the potential to improve the survival and quality of life of patients with relapsed/refractory multiple myeloma (rrMM). In this systematic review and meta-analysis, conducted in accordance with PRISMA guidelines, we aim to provide a concise overview of the latest developments in CAR-T therapy, assess their potential implications for clinical practice, and evaluate their efficacy and safety outcomes based on the most up-to-date evidence. A literature search conducted from 1 January 2019 to 12 July 2023 on Medline/PubMed, Scopus, and Web of Science identified 2273 articles, of which 29 fulfilled the specified criteria for inclusion. Our results offer robust evidence supporting CAR-T cell therapy’s efficacy in rrMM patients, with an encouraging 83.21% overall response rate (ORR). A generally safe profile was observed, with grade ≥ 3 cytokine release syndrome (CRS) at 7.12% and grade ≥ 3 neurotoxicity at 1.37%. A subgroup analysis revealed a significantly increased ORR in patients with fewer antimyeloma regimens, while grade ≥ 3 CRS was more common in those with a higher proportion of high-risk cytogenetics and prior exposure to BCMA therapy.
Full article
(This article belongs to the Special Issue Recent Advances in Immunotherapy of Multiple Myeloma)
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Open AccessReview
Unraveling the Connection: Pain and Endoplasmic Reticulum Stress
by
Ryoko Kawanaka, Hisayo Jin and Tomohiko Aoe
Int. J. Mol. Sci. 2024, 25(9), 4995; https://doi.org/10.3390/ijms25094995 (registering DOI) - 03 May 2024
Abstract
Pain is a complex and multifaceted experience. Recent research has increasingly focused on the role of endoplasmic reticulum (ER) stress in the induction and modulation of pain. The ER is an essential organelle for cells and plays a key role in protein folding
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Pain is a complex and multifaceted experience. Recent research has increasingly focused on the role of endoplasmic reticulum (ER) stress in the induction and modulation of pain. The ER is an essential organelle for cells and plays a key role in protein folding and calcium dynamics. Various pathological conditions, such as ischemia, hypoxia, toxic substances, and increased protein production, may disturb protein folding, causing an increase in misfolding proteins in the ER. Such an overload of the folding process leads to ER stress and causes the unfolded protein response (UPR), which increases folding capacity in the ER. Uncompensated ER stress impairs intracellular signaling and cell function, resulting in various diseases, such as diabetes and degenerative neurological diseases. ER stress may be a critical universal mechanism underlying human diseases. Pain sensations involve the central as well as peripheral nervous systems. Several preclinical studies indicate that ER stress in the nervous system is enhanced in various painful states, especially in neuropathic pain conditions. The purpose of this narrative review is to uncover the intricate relationship between ER stress and pain, exploring molecular pathways, implications for various pain conditions, and potential therapeutic strategies.
Full article
(This article belongs to the Special Issue Protein Quality Control and Integrated Stress Response Related to Pain Disorders)
Open AccessArticle
Unraveling the Mechanisms Involved in the Beneficial Effects of Magnesium Treatment on Skin Wound Healing
by
Yuta Yoshino, Tatsuki Teruya, Chika Miyamoto, Mai Hirose, Satoshi Endo and Akira Ikari
Int. J. Mol. Sci. 2024, 25(9), 4994; https://doi.org/10.3390/ijms25094994 (registering DOI) - 03 May 2024
Abstract
The skin wound healing process consists of hemostatic, inflammatory, proliferative, and maturation phases, with a complex cellular response by multiple cell types in the epidermis, dermis, and immune system. Magnesium is a mineral essential for life, and although magnesium treatment promotes cutaneous wound
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The skin wound healing process consists of hemostatic, inflammatory, proliferative, and maturation phases, with a complex cellular response by multiple cell types in the epidermis, dermis, and immune system. Magnesium is a mineral essential for life, and although magnesium treatment promotes cutaneous wound healing, the molecular mechanism and timing of action of the healing process are unknown. This study, using human epidermal-derived HaCaT cells and human normal epidermal keratinocyte cells, was performed to investigate the mechanism involved in the effect of magnesium on wound healing. The expression levels of epidermal differentiation-promoting factors were reduced by MgCl2, suggesting an inhibitory effect on epidermal differentiation in the remodeling stage of the late wound healing process. On the other hand, MgCl2 treatment increased the expression of matrix metalloproteinase-7 (MMP7), a cell migration-promoting factor, and enhanced cell migration via the MEK/ERK pathway activation. The enhancement of cell migration by MgCl2 was inhibited by MMP7 knockdown, suggesting that MgCl2 enhances cell migration which is mediated by increased MMP7 expression. Our results revealed that MgCl2 inhibits epidermal differentiation but promotes cell migration, suggesting that applying magnesium to the early wound healing process could be beneficial.
Full article
(This article belongs to the Special Issue The Role of Mg Homeostasis in Disease)
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Open AccessArticle
KCTD Proteins Have Redundant Functions in Controlling Cellular Growth
by
Robert Rizk, Dominic Devost, Darlaine Pétrin and Terence E. Hébert
Int. J. Mol. Sci. 2024, 25(9), 4993; https://doi.org/10.3390/ijms25094993 (registering DOI) - 03 May 2024
Abstract
We explored the functional redundancy of three structurally related KCTD (Potassium Channel Tetramerization Domain) proteins, KCTD2, KCTD5, and KCTD17, by progressively knocking them out in HEK 293 cells using CRISPR/Cas9 genome editing. After validating the knockout, we assessed the effects of progressive knockout
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We explored the functional redundancy of three structurally related KCTD (Potassium Channel Tetramerization Domain) proteins, KCTD2, KCTD5, and KCTD17, by progressively knocking them out in HEK 293 cells using CRISPR/Cas9 genome editing. After validating the knockout, we assessed the effects of progressive knockout on cell growth and gene expression. We noted that the progressive effects of knockout of KCTD isoforms on cell growth were most pervasive when all three isoforms were deleted, suggesting some functions were conserved between them. This was also reflected in progressive changes in gene expression. Our previous work indicated that Gβ1 was involved in the transcriptional control of gene expression, so we compared the gene expression patterns between GNB1 and KCTD KO. Knockout of GNB1 led to numerous changes in the expression levels of other G protein subunit genes, while knockout of KCTD isoforms had the opposite effect, presumably because of their role in regulating levels of Gβ1. Our work demonstrates a unique relationship between KCTD proteins and Gβ1 and a global role for this subfamily of KCTD proteins in maintaining the ability of cells to survive and proliferate.
Full article
(This article belongs to the Special Issue Roles of KCTD Proteins in Biological Processes and Diseases: State of the Art and Future Perspectives)
Open AccessArticle
Development of a Static Avascular and Dynamic Vascular Human Skin Equivalent Employing Collagen/Keratin Hydrogels
by
Kameel Zuniga, Neda Ghousifam, Lucy Shaffer, Sean Brocklehurst, Mark Van Dyke, Robert Christy, Shanmugasundaram Natesan and Marissa Nichole Rylander
Int. J. Mol. Sci. 2024, 25(9), 4992; https://doi.org/10.3390/ijms25094992 (registering DOI) - 03 May 2024
Abstract
One of the primary complications in generating physiologically representative skin tissue is the inability to integrate vasculature into the system, which has been shown to promote the proliferation of basal keratinocytes and consequent keratinocyte differentiation, and is necessary for mimicking representative barrier function
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One of the primary complications in generating physiologically representative skin tissue is the inability to integrate vasculature into the system, which has been shown to promote the proliferation of basal keratinocytes and consequent keratinocyte differentiation, and is necessary for mimicking representative barrier function in the skin and physiological transport properties. We created a 3D vascularized human skin equivalent (VHSE) with a dermal and epidermal layer, and compared keratinocyte differentiation (immunomarker staining), epidermal thickness (H&E staining), and barrier function (transepithelial electrical resistance (TEER) and dextran permeability) to a static, organotypic avascular HSE (AHSE). The VHSE had a significantly thicker epidermal layer and increased resistance, both an indication of increased barrier function, compared to the AHSE. The inclusion of keratin in our collagen hydrogel extracellular matrix (ECM) increased keratinocyte differentiation and barrier function, indicated by greater resistance and decreased permeability. Surprisingly, however, endothelial cells grown in a collagen/keratin extracellular environment showed increased cell growth and decreased vascular permeability, indicating a more confluent and tighter vessel compared to those grown in a pure collagen environment. The development of a novel VHSE, which incorporated physiological vasculature and a unique collagen/keratin ECM, improved barrier function, vessel development, and skin structure compared to a static AHSE model.
Full article
(This article belongs to the Special Issue Research Progress on 3D Cultures for Modeling the Microenvironment)
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Open AccessArticle
Influence of Cold Stress on Physiological and Phytochemical Characteristics and Secondary Metabolite Accumulation in Microclones of Juglans regia L.
by
Nina V. Terletskaya, Elvira A. Shadenova, Yuliya A. Litvinenko, Kazhybek Ashimuly, Malika Erbay, Aigerim Mamirova, Irada Nazarova, Nataliya D. Meduntseva, Nataliya O. Kudrina, Nazym K. Korbozova and Erika D. Djangalina
Int. J. Mol. Sci. 2024, 25(9), 4991; https://doi.org/10.3390/ijms25094991 (registering DOI) - 03 May 2024
Abstract
The current study investigated the impact of cold stress on the morphological, physiological, and phytochemical properties of Juglans regia L. (J. regia) using in vitro microclone cultures. The study revealed significant stress-induced changes in the production of secondary antioxidant metabolites. According
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The current study investigated the impact of cold stress on the morphological, physiological, and phytochemical properties of Juglans regia L. (J. regia) using in vitro microclone cultures. The study revealed significant stress-induced changes in the production of secondary antioxidant metabolites. According to gas chromatography–mass spectrometry (GC–MS) analyses, the stress conditions profoundly altered the metabolism of J. regia microclones. Although the overall spectrum of metabolites was reduced, the production of key secondary antioxidant metabolites significantly increased. Notably, there was a sevenfold (7×) increase in juglone concentration. These findings are crucial for advancing walnut metabolomics and enhancing our understanding of plant responses to abiotic stress factors. Additionally, study results aid in identifying the role of individual metabolites in these processes, which is essential for developing strategies to improve plant resilience and tolerance to adverse conditions.
Full article
(This article belongs to the Special Issue Recent Analysis and Applications of Mass Spectrum in Biochemistry 2.0)
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Open AccessArticle
Predicting Transcription Factor Binding Sites with Deep Learning
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Nimisha Ghosh, Daniele Santoni, Indrajit Saha and Giovanni Felici
Int. J. Mol. Sci. 2024, 25(9), 4990; https://doi.org/10.3390/ijms25094990 (registering DOI) - 03 May 2024
Abstract
Prediction of binding sites for transcription factors is important to understand how the latter regulate gene expression and how this regulation can be modulated for therapeutic purposes. A consistent number of references address this issue with different approaches, Machine Learning being one of
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Prediction of binding sites for transcription factors is important to understand how the latter regulate gene expression and how this regulation can be modulated for therapeutic purposes. A consistent number of references address this issue with different approaches, Machine Learning being one of the most successful. Nevertheless, we note that many such approaches fail to propose a robust and meaningful method to embed the genetic data under analysis. We try to overcome this problem by proposing a bidirectional transformer-based encoder, empowered by bidirectional long-short term memory layers and with a capsule layer responsible for the final prediction. To evaluate the efficiency of the proposed approach, we use benchmark ChIP-seq datasets of five cell lines available in the ENCODE repository (A549, GM12878, Hep-G2, H1-hESC, and Hela). The results show that the proposed method can predict TFBS within the five different cell lines very well; moreover, cross-cell predictions provide satisfactory results as well. Experiments conducted across cell lines are reinforced by the analysis of five additional lines used only to test the model trained using the others. The results confirm that prediction across cell lines remains very high, allowing an extensive cross-transcription factor analysis to be performed from which several indications of interest for molecular biology may be drawn.
Full article
(This article belongs to the Special Issue Deep Learning in Bioinformatics and Biological Data Analysis)
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Open AccessArticle
Exploring CDKN1A Upregulation Mechanisms: Insights into Cell Cycle Arrest Induced by NC2603 Curcumin Analog in MCF-7 Breast Cancer Cells
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Felipe Garcia Nishimura, Beatriz Borsani Sampaio, Tatiana Takahasi Komoto, Wanessa Julia da Silva, Mariana Mezencio Gregório da Costa, Gabriela Inforçatti Haddad, Kamila Chagas Peronni, Adriane Feijó Evangelista, Mohammad Hossain, Jonathan R. Dimmock, Brian Bandy, Rene Oliveira Beleboni, Mozart Marins and Ana Lucia Fachin
Int. J. Mol. Sci. 2024, 25(9), 4989; https://doi.org/10.3390/ijms25094989 (registering DOI) - 03 May 2024
Abstract
Breast cancer stands out as one of the most prevalent malignancies worldwide, necessitating a nuanced understanding of its molecular underpinnings for effective treatment. Hormone receptors in breast cancer cells substantially influence treatment strategies, dictating therapeutic approaches in clinical settings, serving as a guide
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Breast cancer stands out as one of the most prevalent malignancies worldwide, necessitating a nuanced understanding of its molecular underpinnings for effective treatment. Hormone receptors in breast cancer cells substantially influence treatment strategies, dictating therapeutic approaches in clinical settings, serving as a guide for drug development, and aiming to enhance treatment specificity and efficacy. Natural compounds, such as curcumin, offer a diverse array of chemical structures with promising therapeutic potential. Despite curcumin’s benefits, challenges like poor solubility and rapid metabolism have spurred the exploration of analogs. Here, we evaluated the efficacy of the curcumin analog NC2603 to induce cell cycle arrest in MCF-7 breast cancer cells and explored its molecular mechanisms. Our findings reveal potent inhibition of cell viability (IC50 = 5.6 μM) and greater specificity than doxorubicin toward MCF-7 vs. non-cancer HaCaT cells. Transcriptome analysis identified 12,055 modulated genes, most notably upregulation of GADD45A and downregulation of ESR1, implicating CDKN1A-mediated regulation of proliferation and cell cycle genes. We hypothesize that the curcumin analog by inducing GADD45A expression and repressing ESR1, triggers the expression of CDKN1A, which in turn downregulates the expression of many important genes of proliferation and the cell cycle. These insights advance our understanding of curcumin analogs’ therapeutic potential, highlighting not just their role in treatment, but also the molecular pathways involved in their activity toward breast cancer cells.
Full article
(This article belongs to the Special Issue Molecular Mechanisms and New Therapies for Breast Cancer)
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Open AccessEditorial
Molecular Insight of Plants Response to Drought Stress: Perspectives and New Insights towards Food Security
by
Isabel Marques and Honghong Hu
Int. J. Mol. Sci. 2024, 25(9), 4988; https://doi.org/10.3390/ijms25094988 (registering DOI) - 03 May 2024
Abstract
In the face of climate-induced challenges, understanding the intricate molecular mechanisms underlying drought tolerance in plants has become imperative [...]
Full article
(This article belongs to the Special Issue Molecular Insight of Plants Response to Drought Stress)
Open AccessArticle
Podocyte-Specific Deletion of MCP-1 Fails to Protect against Angiotensin II- or Adriamycin-Induced Glomerular Disease
by
Corry D. Bondi, Hannah L. Hartman, Brittney M. Rush and Roderick J. Tan
Int. J. Mol. Sci. 2024, 25(9), 4987; https://doi.org/10.3390/ijms25094987 (registering DOI) - 03 May 2024
Abstract
Investigating the role of podocytes in proteinuric disease is imperative to address the increasing global burden of chronic kidney disease (CKD). Studies strongly implicate increased levels of monocyte chemoattractant protein-1 (MCP-1/CCL2) in proteinuric CKD. Since podocytes express the receptor for MCP-1 (i.e., CCR2),
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Investigating the role of podocytes in proteinuric disease is imperative to address the increasing global burden of chronic kidney disease (CKD). Studies strongly implicate increased levels of monocyte chemoattractant protein-1 (MCP-1/CCL2) in proteinuric CKD. Since podocytes express the receptor for MCP-1 (i.e., CCR2), we hypothesized that podocyte-specific MCP-1 production in response to stimuli could activate its receptor in an autocrine manner, leading to further podocyte injury. To test this hypothesis, we generated podocyte-specific MCP-1 knockout mice (Podo-Mcp-1fl/fl) and exposed them to proteinuric injury induced by either angiotensin II (Ang II; 1.5 mg/kg/d, osmotic minipump) or Adriamycin (Adr; 18 mg/kg, intravenous bolus). At baseline, there were no between-group differences in body weight, histology, albuminuria, and podocyte markers. After 28 days, there were no between-group differences in survival, change in body weight, albuminuria, kidney function, glomerular injury, and tubulointerstitial fibrosis. The lack of protection in the knockout mice suggests that podocyte-specific MCP-1 production is not a major contributor to either Ang II- or Adr-induced glomerular disease, implicating that another cell type is the source of pathogenic MCP-1 production in CKD.
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(This article belongs to the Section Molecular Biology)
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The Role of Glutathione Transferase Omega-Class Variant Alleles in Individual Susceptibility to Ovarian Cancer
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Petar Simic, Vesna Coric, Igor Pljesa, Ana Savic-Radojevic, Nebojsa Zecevic, Jovana Kocic, Tatjana Simic, Vladimir Pazin and Marija Pljesa-Ercegovac
Int. J. Mol. Sci. 2024, 25(9), 4986; https://doi.org/10.3390/ijms25094986 (registering DOI) - 03 May 2024
Abstract
The tumor microenvironment is affected by reactive oxygen species and has been suggested to have an important role in ovarian cancer (OC) tumorigenesis. The role of glutathione transferases (GSTs) in the maintenance of redox balance is considered as an important contributing factor in
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The tumor microenvironment is affected by reactive oxygen species and has been suggested to have an important role in ovarian cancer (OC) tumorigenesis. The role of glutathione transferases (GSTs) in the maintenance of redox balance is considered as an important contributing factor in cancer, including OC. Furthermore, GSTs are mostly encoded by highly polymorphic genes, which further highlights their potential role in OC, known to originate from accumulated genetic changes. Since the potential relevance of genetic variations in omega-class GSTs (GSTO1 and GSTO2), with somewhat different activities such as thioltransferase and dehydroascorbate reductase activity, has not been clarified as yet in terms of susceptibility to OC, we aimed to investigate whether the presence of different GSTO1 and GSTO2 genetic variants, individually or combined, might represent determinants of risk for OC development. Genotyping was performed in 110 OC patients and 129 matched controls using a PCR-based assay for genotyping single nucleotide polymorphisms. The results of our study show that homozygous carriers of the GSTO2 variant G allele are at an increased risk of OC development in comparison to the carriers of the referent genotype (OR1 = 2.16, 95% CI: 0.88–5.26, p = 0.08; OR2 = 2.49, 95% CI: 0.93–6.61, p = 0.06). Furthermore, individuals with GST omega haplotype H2, meaning the concomitant presence of the GSTO1*A and GSTO2*G alleles, are more susceptible to OC development, while carriers of the H4 (*A*A) haplotype exhibited lower risk of OC when crude and adjusted haplotype analysis was performed (OR1 = 0.29; 95% CI: 0.12–0.70; p = 0.007 and OR2 = 0.27; 95% CI: 0.11–0.67; p = 0.0054). Overall, our results suggest that GSTO locus variants may confer OC risk.
Full article
(This article belongs to the Special Issue Gynecologic Cancer: From Molecular, Cellular Mechanisms to Novel Therapies)
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Extreme Tolerance of Extraocular Muscles to Diseases and Aging: Why and How?
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Angelina Titova, Sergey Nikolaev, Airat Bilyalov, Nikita Filatov, Sergei Brovkin, Dmitrii Shestakov, Igor Khatkov, Ekaterina Pismennaya, Vyacheslav Bondarev, Margarita Antyuxina, Elena Shagimardanova, Natalia Bodunova and Oleg Gusev
Int. J. Mol. Sci. 2024, 25(9), 4985; https://doi.org/10.3390/ijms25094985 (registering DOI) - 03 May 2024
Abstract
The extraocular muscles (EOMs) possess unique characteristics that set them apart from other skeletal muscles. These muscles, responsible for eye movements, exhibit remarkable resistance to various muscular dystrophies and aging, presenting a significant contrast to the vulnerability of skeletal muscles to these conditions.
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The extraocular muscles (EOMs) possess unique characteristics that set them apart from other skeletal muscles. These muscles, responsible for eye movements, exhibit remarkable resistance to various muscular dystrophies and aging, presenting a significant contrast to the vulnerability of skeletal muscles to these conditions. In this review, we delve into the cellular and molecular underpinnings of the distinct properties of EOMs. We explore their structural complexity, highlighting differences in fiber types, innervation patterns, and developmental origins. Notably, EOM fibers express a diverse array of myosin heavy-chain isoforms, retaining embryonic forms into adulthood. Moreover, their motor innervation is characterized by a high ratio of nerve fibers to muscle fibers and the presence of unique neuromuscular junctions. These features contribute to the specialized functions of EOMs, including rapid and precise eye movements. Understanding the mechanisms behind the resilience of EOMs to disease and aging may offer insights into potential therapeutic strategies for treating muscular dystrophies and myopathies affecting other skeletal muscles.
Full article
(This article belongs to the Special Issue Skeletal Muscle Function and Metabolism: Molecular Mechanisms and Treatment)
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Disuse-Induced Muscle Fatigue: Facts and Assumptions
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Xenia V. Sergeeva, Irina D. Lvova and Kristina A. Sharlo
Int. J. Mol. Sci. 2024, 25(9), 4984; https://doi.org/10.3390/ijms25094984 (registering DOI) - 03 May 2024
Abstract
Skeletal muscle unloading occurs during a wide range of conditions, from space flight to bed rest. The unloaded muscle undergoes negative functional changes, which include increased fatigue. The mechanisms of unloading-induced fatigue are far from complete understanding and cannot be explained by muscle
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Skeletal muscle unloading occurs during a wide range of conditions, from space flight to bed rest. The unloaded muscle undergoes negative functional changes, which include increased fatigue. The mechanisms of unloading-induced fatigue are far from complete understanding and cannot be explained by muscle atrophy only. In this review, we summarize the data concerning unloading-induced fatigue in different muscles and different unloading models and provide several potential mechanisms of unloading-induced fatigue based on recent experimental data. The unloading-induced changes leading to increased fatigue include both neurobiological and intramuscular processes. The development of intramuscular fatigue seems to be mainly contributed by the transformation of soleus muscle fibers from a fatigue-resistant, “oxidative“ “slow” phenotype to a “fast” “glycolytic“ one. This process includes slow-to-fast fiber-type shift and mitochondrial density decline, as well as the disruption of activating signaling interconnections between slow-type myosin expression and mitochondrial biogenesis. A vast pool of relevant literature suggests that these events are triggered by the inactivation of muscle fibers in the early stages of muscle unloading, leading to the accumulation of high-energy phosphates and calcium ions in the myoplasm, as well as NO decrease. Disturbance of these secondary messengers leads to structural changes in muscles that, in turn, cause increased fatigue.
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(This article belongs to the Special Issue Skeletal Muscle Function and Metabolism: Molecular Mechanisms and Treatment)
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Open AccessArticle
Carnosic Acid Inhibits Herpes Simplex Virus Replication by Suppressing Cellular ATP Synthesis
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Georgina Horváth, Edit Molnár, Zoltán Szabó, Gábor Kecskeméti, László Juhász, Szabolcs Péter Tallósy, József Nyári, Anita Bogdanov, Ferenc Somogyvári, Valéria Endrész, Katalin Burián and Dezső P. Virok
Int. J. Mol. Sci. 2024, 25(9), 4983; https://doi.org/10.3390/ijms25094983 (registering DOI) - 03 May 2024
Abstract
Acquiring resistance against antiviral drugs is a significant problem in antimicrobial therapy. In order to identify novel antiviral compounds, the antiviral activity of eight plants indigenous to the southern region of Hungary against herpes simplex virus-2 (HSV-2) was investigated. The plant extracts and
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Acquiring resistance against antiviral drugs is a significant problem in antimicrobial therapy. In order to identify novel antiviral compounds, the antiviral activity of eight plants indigenous to the southern region of Hungary against herpes simplex virus-2 (HSV-2) was investigated. The plant extracts and the plant compound carnosic acid were tested for their effectiveness on both the extracellular and intracellular forms of HSV-2 on Vero and HeLa cells. HSV-2 replication was measured by a direct quantitative PCR (qPCR). Among the tested plant extracts, Salvia rosmarinus (S. rosmarinus) exhibited a 90.46% reduction in HSV-2 replication at the 0.47 μg/mL concentration. Carnosic acid, a major antimicrobial compound found in rosemary, also demonstrated a significant dose-dependent inhibition of both extracellular and intracellular forms of HSV-2. The 90% inhibitory concentration (IC90) of carnosic acid was between 25 and 6.25 μg/mL. Proteomics and high-resolution respirometry showed that carnosic acid suppressed key ATP synthesis pathways such as glycolysis, citrate cycle, and oxidative phosphorylation. Inhibition of oxidative phosphorylation also suppressed HSV-2 replication up to 39.94-fold. These results indicate that the antiviral action of carnosic acid includes the inhibition of ATP generation by suppressing key energy production pathways. Carnosic acid holds promise as a potential novel antiviral agent against HSV-2.
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(This article belongs to the Special Issue Recent Advances in Herpesviruses)
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Emerging Topics in Metal Complexes: Pharmacological Activity
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Agnieszka Ścibior, Manuel Aureliano and Juan Llopis
Int. J. Mol. Sci. 2024, 25(9), 4982; https://doi.org/10.3390/ijms25094982 (registering DOI) - 03 May 2024
Abstract
This Special Issue (SI), ”Emerging Topics in Metal Complexes: Pharmacological Activity”, includes reports updating our knowledge on metals with multidirectional biological properties and metal-containing compounds/complexes for their potential therapeutic applications, with a focus on strategies improving their pharmacological features [...]
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(This article belongs to the Special Issue Emerging Topics in Metal Complexes: Pharmacological Activity)
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A Nanorobotics-Based Approach of Breast Cancer in the Nanotechnology Era
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Anca-Narcisa Neagu, Taniya Jayaweera, Krishan Weraduwage and Costel C. Darie
Int. J. Mol. Sci. 2024, 25(9), 4981; https://doi.org/10.3390/ijms25094981 - 02 May 2024
Abstract
We are living in an era of advanced nanoscience and nanotechnology. Numerous nanomaterials, culminating in nanorobots, have demonstrated ingenious applications in biomedicine, including breast cancer (BC) nano-theranostics. To solve the complicated problem of BC heterogeneity, non-targeted drug distribution, invasive diagnostics or surgery, resistance
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We are living in an era of advanced nanoscience and nanotechnology. Numerous nanomaterials, culminating in nanorobots, have demonstrated ingenious applications in biomedicine, including breast cancer (BC) nano-theranostics. To solve the complicated problem of BC heterogeneity, non-targeted drug distribution, invasive diagnostics or surgery, resistance to classic onco-therapies and real-time monitoring of tumors, nanorobots are designed to perform multiple tasks at a small scale, even at the organelles or molecular level. Over the last few years, most nanorobots have been bioengineered as biomimetic and biocompatible nano(bio)structures, resembling different organisms and cells, such as urchin, spider, octopus, fish, spermatozoon, flagellar bacterium or helicoidal cyanobacterium. In this review, readers will be able to deepen their knowledge of the structure, behavior and role of several types of nanorobots, among other nanomaterials, in BC theranostics. We summarized here the characteristics of many functionalized nanodevices designed to counteract the main neoplastic hallmark features of BC, from sustaining proliferation and evading anti-growth signaling and resisting programmed cell death to inducing angiogenesis, activating invasion and metastasis, preventing genomic instability, avoiding immune destruction and deregulating autophagy. Most of these nanorobots function as targeted and self-propelled smart nano-carriers or nano-drug delivery systems (nano-DDSs), enhancing the efficiency and safety of chemo-, radio- or photodynamic therapy, or the current imagistic techniques used in BC diagnosis. Most of these nanorobots have been tested in vitro, using various BC cell lines, as well as in vivo, mainly based on mice models. We are still waiting for nanorobots that are low-cost, as well as for a wider transition of these favorable effects from laboratory to clinical practice.
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(This article belongs to the Special Issue The Interplay among Biomolecules and Nanomaterials)
Open AccessArticle
Enhanced Electroactive Phases of Poly(vinylidene Fluoride) Fibers for Tissue Engineering Applications
by
Angelika Zaszczyńska, Arkadiusz Gradys, Anna Ziemiecka, Piotr K. Szewczyk, Ryszard Tymkiewicz, Małgorzata Lewandowska-Szumieł, Urszula Stachewicz and Paweł Ł. Sajkiewicz
Int. J. Mol. Sci. 2024, 25(9), 4980; https://doi.org/10.3390/ijms25094980 - 02 May 2024
Abstract
Nanofibrous materials generated through electrospinning have gained significant attention in tissue regeneration, particularly in the domain of bone reconstruction. There is high interest in designing a material resembling bone tissue, and many scientists are trying to create materials applicable to bone tissue engineering
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Nanofibrous materials generated through electrospinning have gained significant attention in tissue regeneration, particularly in the domain of bone reconstruction. There is high interest in designing a material resembling bone tissue, and many scientists are trying to create materials applicable to bone tissue engineering with piezoelectricity similar to bone. One of the prospective candidates is highly piezoelectric poly(vinylidene fluoride) (PVDF), which was used for fibrous scaffold formation by electrospinning. In this study, we focused on the effect of PVDF molecular weight (180,000 g/mol and 530,000 g/mol) and process parameters, such as the rotational speed of the collector, applied voltage, and solution flow rate on the properties of the final scaffold. Fourier Transform Infrared Spectroscopy allows for determining the effect of molecular weight and processing parameters on the content of the electroactive phases. It can be concluded that the higher molecular weight of the PVDF and higher collector rotational speed increase nanofibers’ diameter, electroactive phase content, and piezoelectric coefficient. Various electrospinning parameters showed changes in electroactive phase content with the maximum at the applied voltage of 22 kV and flow rate of 0.8 mL/h. Moreover, the cytocompatibility of the scaffolds was confirmed in the culture of human adipose-derived stromal cells with known potential for osteogenic differentiation. Based on the results obtained, it can be concluded that PVDF scaffolds may be taken into account as a tool in bone tissue engineering and are worth further investigation.
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(This article belongs to the Special Issue The Application of Biomaterials in Bone Tissue Repair and Regeneration)
Open AccessReview
Stem Cell and Regenerative Therapies for the Treatment of Osteoporotic Vertebral Compression Fractures
by
Songzi Zhang, Yunhwan Lee, Yanting Liu, Yerin Yu and Inbo Han
Int. J. Mol. Sci. 2024, 25(9), 4979; https://doi.org/10.3390/ijms25094979 - 02 May 2024
Abstract
Osteoporotic vertebral compression fractures (OVCFs) significantly increase morbidity and mortality, presenting a formidable challenge in healthcare. Traditional interventions such as vertebroplasty and kyphoplasty, despite their widespread use, are limited in addressing the secondary effects of vertebral fractures in adjacent areas and do not
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Osteoporotic vertebral compression fractures (OVCFs) significantly increase morbidity and mortality, presenting a formidable challenge in healthcare. Traditional interventions such as vertebroplasty and kyphoplasty, despite their widespread use, are limited in addressing the secondary effects of vertebral fractures in adjacent areas and do not facilitate bone regeneration. This review paper explores the emerging domain of regenerative therapies, spotlighting stem cell therapy’s transformative potential in OVCF treatment. It thoroughly describes the therapeutic possibilities and mechanisms of action of mesenchymal stem cells against OVCFs, relying on recent clinical trials and preclinical studies for efficacy assessment. Our findings reveal that stem cell therapy, particularly in combination with scaffolding materials, holds substantial promise for bone regeneration, spinal stability improvement, and pain mitigation. This integration of stem cell-based methods with conventional treatments may herald a new era in OVCF management, potentially improving patient outcomes. This review advocates for accelerated research and collaborative efforts to translate laboratory breakthroughs into clinical practice, emphasizing the revolutionary impact of regenerative therapies on OVCF management. In summary, this paper positions stem cell therapy at the forefront of innovation for OVCF treatment, stressing the importance of ongoing research and cross-disciplinary collaboration to unlock its full clinical potential.
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(This article belongs to the Special Issue Musculoskeletal Development and Skeletal Pathophysiologies 2.0)
Open AccessArticle
Tunable Construction of Chiral Nematic Cellulose Nanocrystals/ZnO Films for Ultra-Sensitive, Recyclable Sensing of Humidity and Ethanol
by
Xiao Xiao, Hanqi Dong, Xinxin Ping, Guowei Shan, Jie Chen, Mengxing Yan, Weixing Li and Zhe Ling
Int. J. Mol. Sci. 2024, 25(9), 4978; https://doi.org/10.3390/ijms25094978 - 02 May 2024
Abstract
The investigation of functional materials derived from sustainable and eco-friendly bioresources has generated significant attention. Herein, nanocomposite films based on chiral nematic cellulose crystals (CNCs) were developed by incorporating xylose and biocompatible ZnO nanoparticles (NPs) via evaporation-induced self-assembly (EISA). The nanocomposite films exhibited
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The investigation of functional materials derived from sustainable and eco-friendly bioresources has generated significant attention. Herein, nanocomposite films based on chiral nematic cellulose crystals (CNCs) were developed by incorporating xylose and biocompatible ZnO nanoparticles (NPs) via evaporation-induced self-assembly (EISA). The nanocomposite films exhibited iridescent color changes that corresponded to the birefringence phenomenon under polarized light, which was attributed to the formation of cholesteric structures. ZnO nanoparticles were proved to successfully adjust the helical pitches of the chiral arrangements of the CNCs, resulting in tunable optical light with shifted wavelength bands. Furthermore, the nanocomposite films showed fast humidity and ethanol stimuli response properties, exhibiting the potential of stimuli sensors of the CNC-based sustainable materials.
Full article
(This article belongs to the Special Issue Nanocellulose: Recent Advances and Green Applications)
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