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 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 and Molecular Biology) / CiteScore - Q1 (Organic Chemistry)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 20.5 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the first half of 2025).
- 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 IJMS.
- Companion journals for IJMS include: Biophysica, Stresses, Lymphatics and SynBio.
Impact Factor:
4.9 (2024);
5-Year Impact Factor:
5.7 (2024)
Latest Articles
Advances in Cytoplasmic Male Sterility in Sugar Beet from Mitochondrial Genome Structural Dynamics and Nuclear-Cytoplasmic Coordination
Int. J. Mol. Sci. 2025, 26(20), 10175; https://doi.org/10.3390/ijms262010175 (registering DOI) - 19 Oct 2025
Abstract
Sugar beet (Beta vulgaris L.) is a globally important sugar crop whose hybrid breeding system relies heavily on cytoplasmic male sterility (CMS) lines. Recent advances in sugar beet genomics, particularly the release of high-quality reference genomes and the characterization of organellar genomes,
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Sugar beet (Beta vulgaris L.) is a globally important sugar crop whose hybrid breeding system relies heavily on cytoplasmic male sterility (CMS) lines. Recent advances in sugar beet genomics, particularly the release of high-quality reference genomes and the characterization of organellar genomes, have provided a foundation for elucidating the molecular genetic mechanisms of CMS. Furthermore, innovations in gene editing technologies are enabling transformative functional studies in this field. The precise targeting of CMS-associated mitochondrial genes and nuclear restorer-of-fertility genes not only allows for direct investigation of theoretical models governing fertility regulation through nuclear–cytoplasmic interactions but also holds promise for the targeted development of sterile and restorer lines. This review systematically summarizes progresses in sugar beet genomics, the development of gene editing tools, and the current understanding of the molecular genetics of CMS and fertility restoration in sugar beet. Although challenges remain—such as efficient delivery of editing tools into mitochondria and coordinated editing of multiple genes—the integration of genomic and gene editing technologies is expected to accelerate multi-omics-guided dissection of CMS mechanisms. These advances will facilitate the precise design of high-yield, high-sugar, and stress-resistant sugar beet hybrids, thereby providing core scientific and technological support for the sustainable development of the global sugar industry.
Full article
(This article belongs to the Special Issue Genetics and Breeding for Sugar Crops)
Open AccessReview
The Role of Tenascin-C in Neuroinflammation and Neuroplasticity
by
Ya-Li Jin, Shi-Wen Bao, Meng-Xuan Huang, Yong-Jing Gao, Huan-Jun Lu and Xiao-Bo Wu
Int. J. Mol. Sci. 2025, 26(20), 10174; https://doi.org/10.3390/ijms262010174 (registering DOI) - 19 Oct 2025
Abstract
Tenascin-C (TNC) is a complex extracellular matrix (ECM) protein that plays a critical role in regulating cellular adhesion, motility, proliferation, and inflammation through its interaction with Toll-like receptor 4 (TLR4) and other receptors. The upregulation of TNC is associated with inflammatory responses, autoimmune
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Tenascin-C (TNC) is a complex extracellular matrix (ECM) protein that plays a critical role in regulating cellular adhesion, motility, proliferation, and inflammation through its interaction with Toll-like receptor 4 (TLR4) and other receptors. The upregulation of TNC is associated with inflammatory responses, autoimmune disorders, and neoplastic conditions during both physiological and pathological tissue remodeling. In the central nervous system (CNS), TNC contributes to neuroinflammatory processes by modulating the function of immune cells and the secretion of pro-inflammatory mediators, thereby playing a pivotal role in the initiation and progression of neuroinflammatory diseases. TNC is expressed in astrocytes, neural progenitor cells, and various neuronal populations within both developing and mature CNS regions. It regulates neuronal migration and axonal guidance during neurogenesis, facilitating synaptic plasticity and CNS regeneration. Furthermore, TNC enhances neuroplasticity through interactions with receptor families, such as integrins, to establish the molecular connections necessary for cell communication and signal transduction. This review investigates the mechanistic properties of TNC, focusing on its spatiotemporal expression, molecular interactions with receptors, and its role in neurological disorders, in addition to its modulatory capacity in neuroplastic processes. Additionally, this review delves into recent research advancements with respect to neuroinflammation involving TNC, along with therapeutic strategies targeting TNC.
Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanism in Neuroinflammation Research)
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Open AccessReview
Measuring the Invisible: Microbial Diagnostics for Periodontitis—A Narrative Review
by
Michihiko Usui, Suzuka Miyagi, Rieko Yamanaka, Yuichiro Oka, Kaoru Kobayashi, Tsuyoshi Sato, Kotaro Sano, Satoru Onizuka, Maki Inoue, Wataru Fujii, Masanori Iwasaki, Wataru Ariyoshi, Keisuke Nakashima and Tatsuji Nishihara
Int. J. Mol. Sci. 2025, 26(20), 10172; https://doi.org/10.3390/ijms262010172 (registering DOI) - 19 Oct 2025
Abstract
Periodontitis is a biofilm-driven inflammatory disease in which conventional indices (probing depth, clinical attachment level, and radiographs) quantify tissue destruction without capturing the biology of infection. In this review, we synthesized microbiological diagnostics, from chairside tools to omics. We outline sampling strategies and
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Periodontitis is a biofilm-driven inflammatory disease in which conventional indices (probing depth, clinical attachment level, and radiographs) quantify tissue destruction without capturing the biology of infection. In this review, we synthesized microbiological diagnostics, from chairside tools to omics. We outline sampling strategies and emphasize the quantitative monitoring of bacterial load. Enzymatic assays (e.g., N-benzoyl-DL-arginine-2-naphthylamide hydrolysis assay test) measure functional activity at the point of care. Immunological methods include rapid immunochromatography for Porphyromonas gingivalis and enzyme-linked immunosorbent assay for the high-throughput measurement of bacterial antigens. Molecular platforms encompass quantitative polymerase chain reaction (qPCR) (TaqMan, SYBR, multiplex panels; propidium monoazide quantitative-qPCR for viable cells), checkerboard DNA–DNA hybridization for semi-quantitative community profiling, loop-mediated isothermal amplification (LAMP)/molecular beacon-LAMP for portable isothermal detection, and microarrays. Complementary modalities such as fluorescent in situ hybridization, next-generation sequencing, and Fourier transform infrared spectroscopy provide spatial, ecological, and biochemical resolutions. We discuss the limitations of current approaches, including sampling bias, presence–activity discordance, semi-quantitation, method biases, limited strain/function resolution, low-biomass artifacts, and lack of validated cutoffs. To address these challenges, we propose a pragmatic hybrid strategy: site-specific quantitative panels combined with activity and host-response markers interpreted alongside clinical metrics under standardized quality assurance/quality control. Priorities include outcome-linked thresholds, strain-aware/functional panels, robust point-of-care chemistry, and harmonized protocols to enable personalized periodontal care.
Full article
(This article belongs to the Special Issue Molecular Pathogenesis and Therapeutic Innovations in Oral Diseases)
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Open AccessArticle
DNA Damage Response and Redox Status in the Resistance of Multiple Myeloma Cells to Genotoxic Treatment
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Panagiotis Malamos, Christina Papanikolaou, Elisavet Deligianni, Dimitra Mavroeidi, Konstantinos Koutoulogenis, Maria Gavriatopoulou, Evangelos Terpos and Vassilis L. Souliotis
Int. J. Mol. Sci. 2025, 26(20), 10171; https://doi.org/10.3390/ijms262010171 (registering DOI) - 19 Oct 2025
Abstract
The DNA Damage Response (DDR) network is an essential machinery for maintaining genomic integrity, with DDR defects being implicated in cancer initiation, progression, and treatment resistance. Moreover, oxidative stress, an imbalance between reactive oxygen species production and antioxidant defense, can significantly impact cell
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The DNA Damage Response (DDR) network is an essential machinery for maintaining genomic integrity, with DDR defects being implicated in cancer initiation, progression, and treatment resistance. Moreover, oxidative stress, an imbalance between reactive oxygen species production and antioxidant defense, can significantly impact cell viability, leading to cell death or survival. Herein, we tested the hypothesis that DDR-related signals and redox status measured in multiple myeloma (MM) cell lines correlate with the sensitivity to genotoxic insults. At baseline and following irradiation with Ultraviolet C (UVC; 50 J/m2) or treatment with melphalan (100 μg/mL for 5 min) DDR-related parameters, redox status expressed as GSH/GSSG ratio and apurinic/apyrimidinic sites were evaluated in a panel of eleven human MM cell lines and one healthy B lymphoblastoid cell line. We found that MM cell lines with increased apoptosis rates displayed significantly higher levels of endogenous/baseline DNA damage, reduced GSH/GSSG ratio, augmented apurinic/apyrimidinic lesions, decreased nucleotide excision repair and interstrand crosslinks repair capacities, and highly condensed chromatin structure. Taken together, these findings demonstrate that DDR-related parameters and redox status correlate with the sensitivity of MM cells to DNA-damaging agents, specifically melphalan, and, if further validated, may be exploited as novel sensitive/effective biomarkers.
Full article
(This article belongs to the Section Molecular Biology)
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Open AccessArticle
DD-CC-II: Data Driven Cell–Cell Interaction Inference and Its Application to COVID-19
by
Heewon Park and Satoru Miyano
Int. J. Mol. Sci. 2025, 26(20), 10170; https://doi.org/10.3390/ijms262010170 (registering DOI) - 19 Oct 2025
Abstract
Cell–cell interactions play a pivotal role in maintaining tissue homeostasis and driving disease progression. Conventional Cell–cell interactions modeling approaches depend on ligand–receptor databases, which often fail to capture context-specific or newly emerging signaling mechanisms. To address this limitation, we propose a data-driven computational
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Cell–cell interactions play a pivotal role in maintaining tissue homeostasis and driving disease progression. Conventional Cell–cell interactions modeling approaches depend on ligand–receptor databases, which often fail to capture context-specific or newly emerging signaling mechanisms. To address this limitation, we propose a data-driven computational framework, data-driven cell–cell interaction inference (DD-CC-II), which employs a graph-based model using eigen-cells to represent cell groups. DD-CC-II uses eigen-cells (i.e., functional module within the cell population) to characterize cell groups and construct correlation coefficient networks to model between-group associations. Correlation coefficient networks between eigen-cells are constructed, and their statistical significance is evaluated via over-representation analysis and hypergeometric testing. Monte Carlo simulations demonstrate that DD-CC-II achieves superior performance in inferring CCIs compared with ligand–receptor-based methods. The application to whole-blood RNA-seq data from the Japan COVID-19 Task Force revealed severity stage-specific interaction patterns. Markers such as FOS, CXCL8, and HLA-A were associated with high severity, whereas IL1B, CD3D, and CCL5 were related to low severity. The systemic lupus erythematosus pathway emerged as a potential immune mechanism underlying disease severity. Overall, DD-CC-II provides a data-centric approach for mapping the cellular communication landscape, facilitating a better understanding of disease progression at the intercellular level.
Full article
(This article belongs to the Special Issue Advances in Biomathematics, Computational Biology, and Bioengineering)
Open AccessArticle
Mast Cells, Pancreatic Stellate Cells, and Telocytes in Chronic Pancreatitis: Ultrastructural Study
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Irina Chekmareva, Andrey Kostin, Oksana Paklina, Dmitry Kalinin, Dmitry Suraev, Nikolay Karnaukhov, Alexander Alekhnovich, Atim Emaimo John, Viktoria Shishkina, Igor Buchwalow, Markus Tiemann and Dmitrii Atiakshin
Int. J. Mol. Sci. 2025, 26(20), 10169; https://doi.org/10.3390/ijms262010169 (registering DOI) - 19 Oct 2025
Abstract
Pancreatic inflammation and subsequent fibrosis drive serious disease complications. However, the pathogenesis of this process and the mechanisms underlying excessive extracellular matrix (ECM) deposition remain poorly understood. Our aim was to study intercellular interactions and ultrastructural changes in mast cells, pancreatic stellate cells,
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Pancreatic inflammation and subsequent fibrosis drive serious disease complications. However, the pathogenesis of this process and the mechanisms underlying excessive extracellular matrix (ECM) deposition remain poorly understood. Our aim was to study intercellular interactions and ultrastructural changes in mast cells, pancreatic stellate cells, and telocytes, as well as in the extracellular matrix in various degrees of pancreatic fibrosis. Histological, immunohistochemical, and electron microscopic (EM) studies were performed on surgical materials from 17 patients. Mapping of fibrosis fields was performed on scanned images using the QuPath software v0.6.0. The IHC study was performed using a panel of antibodies: CD34, CD117, and SMA. Fluorescent IHC was performed using a panel of antibodies: CD34 and CD117. The EM study was performed on ultrathin sections with a thickness of 100–120 nm. The functional activity of mast cells (MCs) increased in pancreatic fibrosis. Most of the MCs were in a degranulation state, with the formation of intercellular contacts. The activation of pancreatic stellate cells (PaSCs), which underwent ultrastructural and functional changes in pancreatic fibrosis that developed as a result of chronic pancreatitis (CP), was noted. Multiple plasmolemma discontinuities, telopode shortenings, and nuclear fragmentations were observed among telocytes (TCs). The presence of MCs in the inflammatory infiltrate, as well as the destruction of TCs with the activation of exosomal transport, plays an important role in the pathogenesis of fibrosis in CP and provides a promising therapeutic target for the treatment of this pathology.
Full article
(This article belongs to the Special Issue Roles of Mast Cells in Immune-Induced Diseases)
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Open AccessArticle
Differential Expression of Complement Pathway Components in Unexplained Infertility Versus Male Factor Infertility: Insights from an Exploratory Pilot Study
by
Edwina Brennan, Marya K. E. A. Radhi, Zainab A. A. H. Husain, Thozhukat Sathyapalan, Abu Saleh Md Moin, Alexandra E. Butler and Stephen L. Atkin
Int. J. Mol. Sci. 2025, 26(20), 10168; https://doi.org/10.3390/ijms262010168 (registering DOI) - 19 Oct 2025
Abstract
Complement (C) proteins have been linked to infertility and reproductive outcomes. This study was undertaken to determine the association of complement proteins in non-obese women before in vitro fertilization (IVF) with unexplained infertility (UI) compared to women with male factor infertility (MFI) as
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Complement (C) proteins have been linked to infertility and reproductive outcomes. This study was undertaken to determine the association of complement proteins in non-obese women before in vitro fertilization (IVF) with unexplained infertility (UI) compared to women with male factor infertility (MFI) as controls. We hypothesized that complement protein factors may provide evidence for the underlying mechanism in UI. In this exploratory pilot study, 25 women (UI = 14 and MFI = 11) undergoing IVF had blood drawn on day 21 of the luteal phase. Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was undertaken for 25 complement pathway-related proteins. Student’s t-test was used to compare group means and Pearson’s correlations to examine relationships with complement proteins. Baseline demographics and hormonal parameters did not differ between groups, and parameters of the response following IVF did not differ. In the UI group compared to the MFI group, there were lower levels of properdin (p = 0.03) that may reduce endometrial receptivity and impact follicular development, lower C3a anaphylatoxin des arginine (C3adesArg) (p = 0.02) that may reduce endometrial vascularity, lower C4 (C4) (p = 0.04), indicating reduced alternate pathway activation, and lower C8 (C8) (p = 0.04) that also may affect the endometrium. In UI alone, properdin negatively correlated with high-density lipoprotein cholesterol (HDL-c), and C8 positively correlated with thyroid-stimulating hormone (TSH) and Free-triiodothyronine (Free-T3) (p < 0.05). These preliminary findings indicate reduced complement activity among UI women, warranting further mechanistic investigation.
Full article
(This article belongs to the Special Issue Reproductive Endocrinology Research)
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Open AccessArticle
The Prevalence of Second Neoplasms in Patients with Non-Aldosterone Producing Adrenocortical Lesions
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Paraskevi Tripolitsioti, Ariadni Spyroglou, Odysseas Violetis, Panagiota Konstantakou, Eleni Chouliara, Grigoria Betsi, Konstantinos Iliakopoulos, Eleni Memi, Konstantinos Bramis, Denise Kolomodi, Paraskevi Xekouki, Manousos Konstadoulakis, George Mastorakos and Krystallenia I Alexandraki
Int. J. Mol. Sci. 2025, 26(20), 10167; https://doi.org/10.3390/ijms262010167 (registering DOI) - 19 Oct 2025
Abstract
Over the last few decades, due to improvement in imaging techniques, the increased detection of adrenal incidentalomas is observed. Non-aldosterone producing adrenal adenomas (NAPACAs) often co-exist with second benign or malignant lesions. In the present study, we aimed to assess the presence of
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Over the last few decades, due to improvement in imaging techniques, the increased detection of adrenal incidentalomas is observed. Non-aldosterone producing adrenal adenomas (NAPACAs) often co-exist with second benign or malignant lesions. In the present study, we aimed to assess the presence of second neoplasms, both benign and malignant, in patients with NAPACAs, and to investigate possible correlations with clinical parameters, hormonal characteristics and the emergence of comorbidities. A total of 130 NAPACA patients were included in this single-center retrospective study. In this cohort, 35.4% of NAPACA patients carried any second neoplasm (either benign or malignant) whereas, 26.9% had a second malignant neoplasm. Cortisol levels after 1 mg overnight dexamethasone suppression test (F-ODS) were significantly higher in patients without a second neoplasm (p = 0.02), and this finding was consistent even when categorizing patients with and without malignancies (p = 0.02). In line with this observation, ACTH/F-ODS levels were significantly higher in patients with second malignancies (p < 0.05). Interestingly, the presence of mild autonomous cortisol secretion tended to be lower in patients with second malignancies (p = 0.08). No remarkable differences in the comorbidities of NAPACA patients with and without a second neoplasm were documented. Further prospective studies will be needed to elucidate the role of mild hypercortisolemia on the development of these second tumors in NAPACA patients.
Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in Molecular Pathology, Diagnostics, and Therapeutics)
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Open AccessReview
Redefining Fascia: A Mechanobiological Hub and Stem Cell Reservoir in Regeneration—A Systematic Review
by
Carmelo Pirri, Nina Pirri, Lucia Petrelli, Raffaele De Caro and Carla Stecco
Int. J. Mol. Sci. 2025, 26(20), 10166; https://doi.org/10.3390/ijms262010166 (registering DOI) - 19 Oct 2025
Abstract
Fascia, once considered a passive connective covering, is now recognized as a mechanosensitive tissue and stem cell niche with roles in regeneration, ECM remodeling, and immune–vascular regulation. The aim of this review was to synthetize evidence of fascia-derived progenitors and their mechanobiological functions
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Fascia, once considered a passive connective covering, is now recognized as a mechanosensitive tissue and stem cell niche with roles in regeneration, ECM remodeling, and immune–vascular regulation. The aim of this review was to synthetize evidence of fascia-derived progenitors and their mechanobiological functions across in vitro, preclinical and clinical domains. A systematic search of PubMed, Scopus and Web of Science (up to August 2025) was performed in accordance with PRIMS guidelines. Eligible studies addressed fascia in relation to stem/progenitor cells and regenerative outcomes. Risk of bias was assessed with OHAT criteria for in vitro studies, SYRCLE for animal studies and ROBINS-I for clinical studies. Of 648 records identified, 34 studies were included, encompassing 17 in vitro, 17 animal and 4 clinical investigations, with overlap across domains, and 3 reviews. In vitro, fascia-derived stem cells (FDSCs), FAPs and ASCs were shown to remodel ECM, promote angiogenesis and respond to mechanical cues. Animal models revealed collective fibroblast migration as ECM patches, regulated by N-cadherin, Connexin43 and p120-catenin, while CD201+ progenitors directed scar formation. Clinical studies, though few, reported improved outcomes with subfascial PRP injections and adipofascial flaps. Fascia appears as an active mechanobiological hub and stem cell reservoir that may influence tissue repair and fibrosis, although current evidence, particularly from clinical studies, remains preliminary. Despite promising insights, evidence is limited by methodological heterogeneity, emphasizing the need for mechanistic human studies and well-powered clinical trials.
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(This article belongs to the Section Molecular Biology)
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Open AccessArticle
Pan-Cancer Detection Through DNA Methylation Profiling Using Enzymatic Conversion Library Preparation with Targeted Sequencing
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Alvida Qvick, Emma Adolfsson, Lina Tornéus, Carl Mårten Lindqvist, Jessica Carlsson, Bianca Stenmark, Christina Karlsson and Gisela Helenius
Int. J. Mol. Sci. 2025, 26(20), 10165; https://doi.org/10.3390/ijms262010165 (registering DOI) - 19 Oct 2025
Abstract
We investigated differences in circulating cell-free DNA (cfDNA) methylation between patients with cancer and those presenting with severe, nonspecific symptoms. Plasma cfDNA from 229 patients was analyzed, of whom 37 were diagnosed with a wide spectrum of cancer types within 12 months. Samples
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We investigated differences in circulating cell-free DNA (cfDNA) methylation between patients with cancer and those presenting with severe, nonspecific symptoms. Plasma cfDNA from 229 patients was analyzed, of whom 37 were diagnosed with a wide spectrum of cancer types within 12 months. Samples underwent enzymatic conversion, library preparation, and enrichment using the NEBNext workflow and Twist pan-cancer methylation panel, followed by sequencing. Methylation analysis was performed with nf-core/methylseq. Differentially methylated regions (DMRs) were identified with DMRichR. Machine learning with cross-validation was used to classify cancer and controls. The classifier was applied to an external validation set of 144 controls previously unseen by the model. Cancer samples showed higher overall CpG methylation than controls (1.82% vs. 1.34%, p < 0.001). A total of 162 DMRs were detected, 95.7% being hypermethylated in cancer. Machine learning identified 20 key DMRs for classification between cancer and controls. The final model achieved an AUC of 0.88 (83.8% sensitivity, 83.8% specificity), while mean cross-validation performance reached an AUC of 0.73 (57.1% sensitivity, 77.5% specificity). The specificity of the classifier on unseen control samples was 79.2%. Distinct methylation differences and DMR-based classification support cfDNA methylation as a robust biomarker for cancer detection in patients with confounding conditions.
Full article
(This article belongs to the Special Issue Molecular Research on Epigenetic Modifications)
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Open AccessArticle
Comprehensive Transcriptomic Analysis of the Molecular Mechanisms Conferring Resistance to Rice Blast in the Elite Restorer Line Fuhui2165
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Shuijin Zhang, Yinyin Mao, Yonghe Hong, Feiyan Zheng, Ronghua Hu, Shihang Tu, Fantao Zhang and Peng Zhou
Int. J. Mol. Sci. 2025, 26(20), 10164; https://doi.org/10.3390/ijms262010164 (registering DOI) - 19 Oct 2025
Abstract
Rice blast, caused by Magnaporthe oryzae (M. oryzae), severely threatens global rice production with substantial yield losses, endangering food security and driving demand for resistant varieties. Fuhui2165 (FH2165), an elite restorer line with stable blast resistance, superior agronomic traits, and high
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Rice blast, caused by Magnaporthe oryzae (M. oryzae), severely threatens global rice production with substantial yield losses, endangering food security and driving demand for resistant varieties. Fuhui2165 (FH2165), an elite restorer line with stable blast resistance, superior agronomic traits, and high grain quality, is valuable for hybrid breeding, but its resistance mechanisms remain unclear. In this study, we investigated the rice blast resistance and underlying mechanisms in FH2165 and its parental lines (Huahangsimiao/HHSM, Minghui86/MH86, and Shuhui527/SH527) using transcriptome sequencing analysis. Phenotypic analysis revealed that FH2165 and HHSM exhibited stronger resistance compared to MH86 and SH527. Differential expression analysis identified 3886, 2513, 3390, and 4678 differentially expressed genes (DEGs) in FH2165, HHSM, MH86, and SH527, respectively. Gene Ontology (GO) enrichment analysis highlighted DEGs associated with chloroplasts, plastids, thylakoids, and related cellular components. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified significant enrichment in pathways such as carbon metabolism, amino acid biosynthesis, and photosynthesis. This suggested that defense strategies could involve energy reprogramming and the synthesis of secondary metabolites. Additionally, the DEGs co-expressed specifically in FH2165 and HHSM were enriched in functions related to RNA processing, GTP binding, and L-ascorbic acid binding, with purine metabolism playing a role in the regulation of energy and signaling. These findings elucidated the critical metabolic and signaling networks that underlie the blast resistance of FH2165 and offered potential targets for breeding high-yield, disease-resistant hybrid rice varieties.
Full article
(This article belongs to the Special Issue Plant Stress Biology)
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Open AccessReview
Microbial-Based Green Synthesis of Silver Nanoparticles: A Comparative Review of Bacteria- and Fungi-Mediated Approaches
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Emir Akdaşçi, Furkan Eker, Hatice Duman, Mikhael Bechelany and Sercan Karav
Int. J. Mol. Sci. 2025, 26(20), 10163; https://doi.org/10.3390/ijms262010163 (registering DOI) - 19 Oct 2025
Abstract
The growing demand for sustainable and eco-friendly technologies has driven the development of green and bio-based synthesis methods for metallic nanoparticles. Among these, the microbial synthesis of silver nanoparticles (AgNPs) has emerged as a promising alternative to conventional chemical methods, which often rely
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The growing demand for sustainable and eco-friendly technologies has driven the development of green and bio-based synthesis methods for metallic nanoparticles. Among these, the microbial synthesis of silver nanoparticles (AgNPs) has emerged as a promising alternative to conventional chemical methods, which often rely on hazardous reagents and harsh conditions. Bacteria and fungi are particularly attractive due to their ability to produce AgNPs with tunable size, shape, and surface properties through natural enzymatic and metabolic processes. This review provides a comparative analysis of bacterial and fungal synthesis routes, focusing on their distinct advantages, limitations, and optimal applications. Bacterial synthesis offers faster growth, simpler culture requirements, and greater potential for genetic manipulation, enabling precise control over nanoparticle (NP) characteristics. In contrast, fungal synthesis typically yields higher nanoparticle stability and is well suited for extracellular, scalable production. The review also summarizes key synthesis parameters (e.g., pH, temperature, reaction time), addresses reproducibility and scalability challenges, and highlights emerging research areas, including antibacterial bio-hybrid materials and bacterial-supported metallic catalysts. Overall, this comparative perspective provides a clear framework for selecting appropriate microbial systems for different technological applications and identifies future research directions to advance green nanotechnology.
Full article
(This article belongs to the Special Issue Innovative Nanomaterials from Functional Molecules)
Open AccessReview
IL-31/33 Axis in Atopic Dermatitis
by
Julia Łacwik, Krzysztof Kraik, Julia Laska, Maciej Tota, Łukasz Sędek and Krzysztof Gomułka
Int. J. Mol. Sci. 2025, 26(20), 10162; https://doi.org/10.3390/ijms262010162 (registering DOI) - 19 Oct 2025
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by impaired epidermal barrier function, immune dysregulation (e.g., Th2 polarization), genetic factors (e.g., filaggrin mutations), environmental triggers and microbial dysbiosis, leading to pruritus and eczematous lesions. In this review, we present the synergistic
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Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by impaired epidermal barrier function, immune dysregulation (e.g., Th2 polarization), genetic factors (e.g., filaggrin mutations), environmental triggers and microbial dysbiosis, leading to pruritus and eczematous lesions. In this review, we present the synergistic “IL-31/IL-33 axis.” IL-33, released by damaged keratinocytes, acts as an alarmin, initiating inflammation via ST2 receptors and promoting Th2 cytokine production (IL-4, IL-5, IL-13). This upregulates IL-31, primarily from Th2 cells, which directly activates sensory neurons to induce pruritus and impairs keratinocyte differentiation. Together, IL-31 and IL-33 exacerbate the itch–scratch feedback loop, barrier disruption, and inflammation. Elevated levels of IL-31 and IL-33 correlate with disease severity. Targeting the IL-31/IL-33 axis represents an emerging therapeutic option, e.g., nemolizumab (anti-IL-31RA) significantly reduces pruritus and AD symptoms in clinical trials. However, anti-IL-33/ST2 agents (e.g., etokimab, tozorakimab) demonstrate variable efficacy, highlighting complexity in targeting IL-33. Future research should prioritize biomarker-driven patient stratification to optimize the clinical application of these novel antibody-based therapies.
Full article
(This article belongs to the Special Issue Molecular Research in Asthma and Allergy)
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Open AccessArticle
Berberine Alleviates Intestinal Inflammation by Disrupting Pathological Macrophage–Epithelial Crosstalk in Macrophage–Organoid Co-Culture Model
by
Yuncong Han, Mengting Li, Tian Chen, Chen Wang, Hong Zhou, Tunan Zhou, Runqing Jia, Ying Chen and Qin Hu
Int. J. Mol. Sci. 2025, 26(20), 10161; https://doi.org/10.3390/ijms262010161 (registering DOI) - 19 Oct 2025
Abstract
Berberine (BBR), a benzylisoquinoline alkaloid isolated from Chinese herb Coptis chinensis, has been widely used clinically to treat intestinal infectious diseases. Recently, it has been found to have multiple pharmacological effects, including anti-inflammatory activity and immune effects in inflammatory bowel disease (IBD).
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Berberine (BBR), a benzylisoquinoline alkaloid isolated from Chinese herb Coptis chinensis, has been widely used clinically to treat intestinal infectious diseases. Recently, it has been found to have multiple pharmacological effects, including anti-inflammatory activity and immune effects in inflammatory bowel disease (IBD). However, its exact targets remain to be elucidated. In this study, we used a mouse intestinal organoid–macrophage co-culture model to investigate the anti-inflammatory effects and immune effects of BBR. Our findings demonstrated that lipopolysaccharide (LPS) induced more robust inflammatory responses and epithelium damage in the co-culture system compared to the organoid alone. BBR effectively attenuated inflammation and restored epithelial barrier integrity by suppressing M1 macrophage polarisation and infiltration, alongside upregulating the expression and organisation of tight junction protein zonula occludens-1 (ZO-1). RNA sequencing and proteomic analysis revealed that BBR disrupted organoid–macrophage interaction by inhibiting chemokine (e.g., C-X-C motif chemokine ligand 1 (CXCL1) and macrophage migration inhibitory factor (MIF)) release from epithelial cells, thereby reducing macrophage recruitment. Collectively, our study establishes the organoid–macrophage co-culture system as a more physiologically relevant model for studying epithelial–immune interactions and elucidates the multi-target mechanism of BBR, which concurrently modulates epithelial cells, macrophages, and their crosstalk. These findings lay the foundation for further exploration of the therapeutic potential of BBR in inflammatory bowel disease and the development of targeted therapies that regulate cell interactions.
Full article
(This article belongs to the Special Issue Natural Compounds in Immune-Inflammatory Regulation: Mechanisms and Therapeutics)
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Open AccessArticle
Heart Under Pressure: Divergent Cardiac Molecules Responses to Azathioprine and Anti-TNF Therapy in Ulcerative Colitis
by
Mirjana Cvetković, Stefan Simović, Dušan Radojević, Mladen Maksić, Nataša Zdravković, Bojan Milošević, Bojan Stojanović, Radojica Stolić, Željko Todorović, Anđela Gogić, Nebojša Zdravković and Mateja Zdravković
Int. J. Mol. Sci. 2025, 26(20), 10160; https://doi.org/10.3390/ijms262010160 (registering DOI) - 19 Oct 2025
Abstract
The treatment of moderate-to-severe ulcerative colitis often requires escalation from 5-ASA therapy to immunosuppressants or biologic agents. However, the effects of azathioprine and anti-TNF therapies on cardiac status and associated biomolecules remain insufficiently studied. In this prospective observational study, we included 84 patients
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The treatment of moderate-to-severe ulcerative colitis often requires escalation from 5-ASA therapy to immunosuppressants or biologic agents. However, the effects of azathioprine and anti-TNF therapies on cardiac status and associated biomolecules remain insufficiently studied. In this prospective observational study, we included 84 patients with moderate-to-severe ulcerative colitis, divided into three treatment groups based on the therapy received (azathioprine, infliximab, or adalimumab), along with 25 healthy controls. Levels of proBNP, NT-proBNP, creatine kinase (CK), CK-MB, and high-sensitivity troponin I (hsTnI) were measured at baseline, 6 h after treatment initiation, and after 3 months of therapy. Troponin levels did not significantly change across the three time points in any treatment group. In contrast, levels of proBNP, NT-proBNP, CK, and CK-MB significantly decreased after 3 months in patients treated with biologics, whereas a significant increase was observed in the azathioprine group. Further prospective trials are needed to adequately assess the cardiac safety of these therapies, particularly in patients with preexisting cardiac impairment.
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(This article belongs to the Special Issue Molecular Mechanisms in Cardiovascular Disease Progression)
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Open AccessArticle
AlphaFold Prediction of Protein–Protein Interactions in the Flaviviridae Proteomes
by
Wahyu Surya, Justin Goh, Caleb Ponniah and Jaume Torres
Int. J. Mol. Sci. 2025, 26(20), 10159; https://doi.org/10.3390/ijms262010159 (registering DOI) - 19 Oct 2025
Abstract
The family Flaviviridae is divided into flaviviruses, hepaciviruses and pestiviruses. Its members infect a wide range of organisms, from insects to humans, and share a similar genome organization where proteins require sequential cleavage from a single translated polyprotein. Despite decades of study, the
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The family Flaviviridae is divided into flaviviruses, hepaciviruses and pestiviruses. Its members infect a wide range of organisms, from insects to humans, and share a similar genome organization where proteins require sequential cleavage from a single translated polyprotein. Despite decades of study, the structures of some non-structural (NS) membrane proteins, or details of their protein–protein interactions (PPIs), are still unclear. Since AlphaFold (AF) can be used to predict interactions between protein domains using Predicted Alignment Error (PAE) score plots, we hypothesized that AF-predicted interactions between domains of complete viral polyproteins can represent PPIs if these interactions are retained once the different proteins are sequentially cleaved. We complemented this approach using AF predictions involving all independent separate protein sequences, instead of using a single polyprotein. We found that most of these PPIs have already been reported experimentally, which validates the use of AF in this context, but not all of these PPIs have been characterized from a structural perspective. Thus, we propose that AF provides testable hypotheses regarding residues involved in these PPIs, and that comparison of the three genera in this family may provide much needed clues to the function of these proteins during the viral life cycle.
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(This article belongs to the Section Molecular Biology)
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Inhibitory Effect of Boesenbergia rotunda and Its Major Flavonoids, Pinostrobin and Pinocembrin on Carbohydrate Digestive Enzymes and Intestinal Glucose Transport in Caco-2 Cells
by
Sathid Aimjongjun, Nopawit Khamto, Vanatsanan Buangamdee, Thanet Sornda, Jukkarin Srivilai and Nanteetip Limpeanchob
Int. J. Mol. Sci. 2025, 26(20), 10158; https://doi.org/10.3390/ijms262010158 (registering DOI) - 19 Oct 2025
Abstract
Boesenbergia rotunda (L.) Mansf., commonly known as fingerroot or “Kra-Chai,” is a traditional Thai medicinal plant used for treating digestive and metabolic disorders. Recent evidence highlights its potential role in controlling hyperglycemia, though its active compounds and mechanisms remain unclear. This study evaluated
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Boesenbergia rotunda (L.) Mansf., commonly known as fingerroot or “Kra-Chai,” is a traditional Thai medicinal plant used for treating digestive and metabolic disorders. Recent evidence highlights its potential role in controlling hyperglycemia, though its active compounds and mechanisms remain unclear. This study evaluated the antidiabetic activity of B. rotunda crude extract and its major flavonoids, pinostrobin and pinocembrin, through in vitro enzyme inhibition and cellular glucose transport assays. Pinocembrin exhibited the strongest inhibition of both α-amylase and α-glucosidase, while pinostrobin and the crude extract showed moderate effects. In Caco-2 cells, the crude extract reduced glucose uptake, whereas both flavonoids markedly inhibited transport under glucose-depleted conditions, suggesting interaction with sodium-dependent glucose transporters (SGLTs). Under high-glucose conditions, their effects were minimal, indicating limited activity on facilitative glucose transporters (GLUTs). Moreover, molecular docking studies revealed that pinostrobin and pinocembrin bind within the glucose transporter channels of SGLT1 and SGLT2, blocking glucose passage and supporting the experimental findings. Overall, B. rotunda, particularly pinocembrin, demonstrates notable in vitro antidiabetic potential through enzyme inhibition and SGLT modulation. Further in vivo investigations are warranted to validate its hypoglycemic properties and identify additional active compounds.
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(This article belongs to the Special Issue Plant-Derived Bioactives: Antioxidant Mechanisms and Preventive Health Strategies)
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PPAR-γ Inhibits Chronic Apical Periodontitis by Facilitating Macrophage Efferocytosis
by
Yuting Wang, Mingfei Wang, Xiaowen Jia, Yifei Tang, Jiayi Wang, Wenjiao Zhang, Tiezhou Hou and Xiaoyue Guan
Int. J. Mol. Sci. 2025, 26(20), 10157; https://doi.org/10.3390/ijms262010157 (registering DOI) - 19 Oct 2025
Abstract
This study aimed to elucidate the role of peroxisome proliferator-activated receptor-γ (PPAR-γ) in regulating macrophage efferocytosis during the pathogenesis of chronic apical periodontitis (CAP). Clinical specimens, rat periapical lesion models, and an in vitro model simulating the CAP inflammatory milieu were employed to
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This study aimed to elucidate the role of peroxisome proliferator-activated receptor-γ (PPAR-γ) in regulating macrophage efferocytosis during the pathogenesis of chronic apical periodontitis (CAP). Clinical specimens, rat periapical lesion models, and an in vitro model simulating the CAP inflammatory milieu were employed to examine the contribution of PPAR-γ to efferocytosis throughout disease progression. The expression of PPAR-γ in vivo was assessed by single-cell RNA sequencing and immunohistochemical (IHC) staining. Pearson’s correlation and linear trend tests were conducted to investigate the association between PPAR-γ and macrophage efferocytosis during CAP progression. Pharmacological modulation of PPAR-γ was further conducted using rosiglitazone (RSG) as an agonist and GW9662 as an antagonist, followed by an assessment of efferocytosis-related parameters and inflammatory responses. Both clinical specimens and animal models demonstrated a progressive reduction in PPAR-γ expression and macrophage efferocytosis during CAP. Notably, PPAR-γ attenuated efferocytosis impairment and significantly reduced pathogen-induced inflammatory responses in macrophages. These findings indicate that defective macrophage efferocytosis contributes to the exacerbation of CAP severity, whereas targeting PPAR-γ may represent a promising therapeutic strategy to alleviate inflammation in periapical lesions by restoring efferocytic capacity. Collectively, this study highlights PPAR-γ as a potential therapeutic target warranting further investigation in CAP treatment.
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(This article belongs to the Section Biochemistry)
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Discovery of a Novel Antithrombotic Cystine Knot Peptide from Spider Venom Gland Transcriptome
by
Jinai Gao, Di Yang, Wanting Wang, Xiaoshan Huang, Ruiyin Guo, Kaixun Cao, Qiumin Lu, Ziyi Wang, Ren Lai and Juan Li
Int. J. Mol. Sci. 2025, 26(20), 10154; https://doi.org/10.3390/ijms262010154 (registering DOI) - 19 Oct 2025
Abstract
The development of effective anticoagulants remains a critical need in modern medicine, particularly for preventing and treating thromboembolic disorders, such as arterial thrombosis and deep vein thrombosis (DVT), as well as complications like ischemic stroke. This study identifies a cysteine-knotted peptide GC38 (sequence:
[...] Read more.
The development of effective anticoagulants remains a critical need in modern medicine, particularly for preventing and treating thromboembolic disorders, such as arterial thrombosis and deep vein thrombosis (DVT), as well as complications like ischemic stroke. This study identifies a cysteine-knotted peptide GC38 (sequence: GCSGKGARCAPSKCCSGLSCGRHGGNMYKSCEWNWKTG) derived from the venom gland transcriptome of the Macrothele sp. spider, which exerts thrombus-inhibitory effects by potentiating activated protein C (APC) activity. In vitro assays reveal that GC38 enhances APC activity, prolongs plasma clotting time, and shows no significant cytotoxicity or hemolytic activity. Mechanistically, GC38 interacts allosterically with APC; biolayer interferometry (BLI) confirms this direct interaction, with a dissociation constant KD of 6.16 μM. Additionally, three in vivo thrombosis models (FeCl3-induced arterial occlusion, stasis-induced DVT, and cortical photothrombotic stroke) consistently demonstrated that GC38 was effective in alleviating thrombus formation, with tail-bleeding assays confirming its low hemorrhagic risk. Collectively, our findings position GC38 as a pioneering spider venom-derived lead molecule that addresses dual arterial and venous antithrombotic actions. This opens new avenues for developing spider venom-derived peptides as therapeutic agents targeting intravascular coagulation in arteries and veins.
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(This article belongs to the Special Issue Molecular Mechanisms of Animal Toxins, Venoms and Antivenoms 2.0)
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Parameters of Micro- and Macrocirculation in Young Uncomplicated Type 1 Diabetic Patients—The Role of Metabolic Memory
by
Jolanta Neubauer-Geryk, Małgorzata Myśliwiec, Katarzyna Zorena and Leszek Bieniaszewski
Int. J. Mol. Sci. 2025, 26(20), 10156; https://doi.org/10.3390/ijms262010156 (registering DOI) - 18 Oct 2025
Abstract
In the current study, we focus on analyzing the relationship between changes in micro- and macrocirculation and different stages of metabolic memory. We hypothesized that early poor glycemic control induces lasting endothelial changes detectable in pediatric type 1 diabetes (T1D) microcirculation. We assessed
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In the current study, we focus on analyzing the relationship between changes in micro- and macrocirculation and different stages of metabolic memory. We hypothesized that early poor glycemic control induces lasting endothelial changes detectable in pediatric type 1 diabetes (T1D) microcirculation. We assessed microcirculation structure and function using capillaroscopy, transcutaneous oxygen pressure (TcPO2), and optical coherence tomography (OCT). We evaluated macrovascular circulation using pulsatility index (PI), ankle-brachial index (ABI) and pulse pressure (PP). We also examined the relationship between circulation parameters, the age at onset, and diabetes duration. The study included 67 patients with uncomplicated type 1. We divided all patients into four groups based on their HbA1c levels at T1D onset and their average HbA1c after one and two years. We assessed the concentrations of TNF-α, IL-35, IL-4, IL-10, IL-18, IL-12, serum angiogenin, VEGF, sVCAM-1, ICAM-1, sP-Selectin, AGEs, and sRAGE. We compared subgroups with different levels of metabolic memory but comparable T1D duration and age at diagnosis. Micro- and macrovascular parameters were similar between the groups. Our comparison of subgroups with identical metabolic memory but different durations and ages at diagnosis revealed clear differences. The subgroup with a shorter T1D duration showed higher capillary density and a smaller inter-capillary distance compared to those with a longer diabetes duration. This subgroup with shorter duration had significantly lower AGE levels and a reduced TNF-α/IL-35 ratio, along with higher levels of IL-35, IL-4, and IL-12, compared to the longer-duration group. Our findings indicate that in youths with uncomplicated T1D, disease duration—not metabolic memory—plays a dominant role in early microvascular alterations.
Full article
(This article belongs to the Special Issue Molecular Research on Type 1 Diabetes and Its Complications: 2nd Edition)
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