-
Mouse Models of HIV-Associated Atherosclerosis
-
Chronic Antibody-Mediated Rejection and Plasma Cell ER Stress: Opportunities and Challenges with Calcineurin Inhibitors
-
Microenvironmental Drivers of Glioma Progression
-
A Novel Insight into the Role of Obesity-Related Adipokines in Ovarian Cancer—State-of-the-Art Review and Future Perspectives
-
The Triad of Blood–Brain Barrier Integrity: Endothelial Cells, Astrocytes, and Pericytes in Perinatal Stroke Pathophysiology
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 (Inorganic Chemistry)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 16.8 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 2024).
- 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, Stresses, Lymphatics and SynBio.
Impact Factor:
4.9 (2023);
5-Year Impact Factor:
5.6 (2023)
Latest Articles
Identification and Functional Exploration of the ALKBH Gene Family in Oriental Melon Fruit Ripening
Int. J. Mol. Sci. 2025, 26(9), 4254; https://doi.org/10.3390/ijms26094254 (registering DOI) - 29 Apr 2025
Abstract
N6-methyladenosine (m6A) methylation functions as a vital post-transcriptional and epigenetic modification in higher plants regulated by α-ketoglutarate-dependent dioxygenases (ALKBH). However, the role of ALKBH genes in oriental melon (Cucumis melo L.) fruit ripening has not been explored. Therefore, we treated
[...] Read more.
N6-methyladenosine (m6A) methylation functions as a vital post-transcriptional and epigenetic modification in higher plants regulated by α-ketoglutarate-dependent dioxygenases (ALKBH). However, the role of ALKBH genes in oriental melon (Cucumis melo L.) fruit ripening has not been explored. Therefore, we treated oriental melon with an exogenous m6A demethylase inhibitor (mechlorfenamic acid) then analyzed endogenous ethylene production and ripening-related indicators to explore the effects of m6A methylation on ripening. Bioinformatics and real-time quantitative PCR analyses were used to determine the impact of ALKBH genes on key ethylene synthesis gene expression. Treatment effectively inhibited endogenous ethylene production, firmness changes, and soluble solid contents, thereby extending fruit ripening. Eight ALKBH gene family members belonging to five major groups were identified in the melon genome. All members were expressed in ripening fruits, with different expression patterns during ripening. CmALKBH6, CmALKBH7, and CmALKBH8 expression was inhibited by an ethylene inhibitor (1-methylcyclopropene). The transient overexpression (OE) of CmALKBH8 in oriental melon led to the increased expression of the ethylene synthesis genes CmACS1, CmACS2, and CmACO1. In summary, the ethylene-regulated gene CmALKBH8 may participate in oriental melon fruit ripening regulation by modulating the methylation levels of ethylene synthesis-related genes. These findings help us better understand how m6A methylation regulates melon ripening.
Full article
(This article belongs to the Section Molecular Plant Sciences)
►
Show Figures
Open AccessArticle
Inorganic Arsenic Induces Elevated p53 Levels with Altered Functionality Impacting the Expression of Toll-like Receptor 3 and Other Target Genes in Immortalized Prostate Epithelial Cells
by
Nancy C. Pacheco-Castillo, Jesús Gómez-Montalvo, Vanesa Olivares-Illana, Félix Recillas-Targa, Erik J. Tokar, S. Eréndira Avendaño-Vázquez and Claudia Escudero-Lourdes
Int. J. Mol. Sci. 2025, 26(9), 4253; https://doi.org/10.3390/ijms26094253 (registering DOI) - 29 Apr 2025
Abstract
Prostate cancer (PCa) is a major global health concern, particularly in advanced stages where chemotherapy resistance and androgen-independent tumor growth reduce survival rates to below 30%. Toll-like receptor 3 (TLR3), regulated by tumor suppressor p53, is a promising therapeutic target due to its
[...] Read more.
Prostate cancer (PCa) is a major global health concern, particularly in advanced stages where chemotherapy resistance and androgen-independent tumor growth reduce survival rates to below 30%. Toll-like receptor 3 (TLR3), regulated by tumor suppressor p53, is a promising therapeutic target due to its role in tumor cell apoptosis. However, chronic exposure to inorganic arsenic (iAs), a known carcinogen, has been linked to PCa progression and reduced TLR3 expression and activation by polyinosinic/polycytidylic acid (Poly(I/C)), a synthetic ligand used in PCa immunotherapy. Here, we demonstrate that chronic sodium arsenite (NaAsO) exposure increases p53 transcript and protein levels in immortalized prostate epithelial cells. Despite this, key p53 target genes, including TLR3, CDKN1A, and BAX, were significantly downregulated, indicating a transcriptionally inactive p53. Chromatin immunoprecipitation (ChIP) confirmed diminished p53 binding to TLR3 and CDKN1A promoters, while sequencing ruled out TP53 mutations. A bioinformatic analysis revealed elevated TP53 but reduced TLR3 and CDKN1A in prostate adenocarcinoma, suggesting that iAs-induced oxidative stress disrupts p53 function. These findings reveal a novel mechanism by which iAs promotes PCa progression through impaired p53 activity, highlighting the need to explore post-translational and epigenetic factors affecting p53. Restoring p53 transcriptional activity may offer a therapeutic strategy for PCa patients exposed to NaAsO.
Full article
(This article belongs to the Section Molecular Biology)
►▼
Show Figures

Graphical abstract
Open AccessPerspective
Alzheimer’s Is a Multiform Disease of Sustained Neuronal Integrated Stress Response Driven by the C99 Fragment Generated Independently of AβPP; Proteolytic Production of Aβ Is Suppressed in AD-Affected Neurons: Evolution of a Theory
by
Vladimir Volloch and Sophia Rits-Volloch
Int. J. Mol. Sci. 2025, 26(9), 4252; https://doi.org/10.3390/ijms26094252 (registering DOI) - 29 Apr 2025
Abstract
The present Perspective analyzes the remarkable evolution of the Amyloid Cascade Hypothesis 2.0 (ACH2.0) theory of Alzheimer’s disease (AD) since its inception a few years ago, as reflected in the diminishing role of amyloid-beta (Aβ) in the disease. In the initial iteration of
[...] Read more.
The present Perspective analyzes the remarkable evolution of the Amyloid Cascade Hypothesis 2.0 (ACH2.0) theory of Alzheimer’s disease (AD) since its inception a few years ago, as reflected in the diminishing role of amyloid-beta (Aβ) in the disease. In the initial iteration of the ACH2.0, Aβ-protein-precursor (AβPP)-derived intraneuronal Aβ (iAβ), accumulated to neuronal integrated stress response (ISR)-eliciting levels, triggers AD. The neuronal ISR, in turn, activates the AβPP-independent production of its C99 fragment that is processed into iAβ, which drives the disease. The second iteration of the ACH2.0 stemmed from the realization that AD is, in fact, a disease of the sustained neuronal ISR. It introduced two categories of AD—conventional and unconventional—differing mainly in the manner of their causation. The former is caused by the neuronal ISR triggered by AβPP-derived iAβ, whereas in the latter, the neuronal ISR is elicited by stressors distinct from AβPP-derived iAβ and arising from brain trauma, viral and bacterial infections, and various types of inflammation. Moreover, conventional AD always contains an unconventional component, and in both forms, the disease is driven by iAβ generated independently of AβPP. In its third, the current, iteration, the ACH2.0 posits that proteolytic production of Aβ is suppressed in AD-affected neurons and that the disease is driven by C99 generated independently of AβPP. Suppression of Aβ production in AD seems an oxymoron: Aβ is equated with AD, and the later is inconceivable without the former in an ingrained Amyloid Cascade Hypothesis (ACH)-based notion. But suppression of Aβ production in AD-affected neurons is where the logic leads, and to follow it we only need to overcome the inertia of the preexisting assumptions. Moreover, not only is the generation of Aβ suppressed, so is the production of all components of the AβPP proteolytic pathway. This assertion is not a quantum leap (unless overcoming the inertia counts as such): the global cellular protein synthesis is severely suppressed under the neuronal ISR conditions, and there is no reason for constituents of the AβPP proteolytic pathway to be exempted, and they, apparently, are not, as indicated by the empirical data. In contrast, tau protein translation persists in AD-affected neurons under ISR conditions because the human tau mRNA contains an internal ribosomal entry site in its 5′UTR. In current mouse models, iAβ derived from AβPP expressed exogenously from human transgenes elicits the neuronal ISR and thus suppresses its own production. Its levels cannot principally reach AD pathology-causing levels regardless of the number of transgenes or the types of FAD mutations that they (or additional transgenes) carry. Since the AβPP-independent C99 production pathway is inoperative in mice, the current transgenic models have no potential for developing the full spectrum of AD pathology. What they display are only effects of the AβPP-derived iAβ-elicited neuronal ISR. The paper describes strategies to construct adequate transgenic AD models. It also details the utilization of human neuronal cells as the only adequate model system currently available for conventional and unconventional AD. The final alteration of the ACH2.0, introduced in the present Perspective, is that AβPP, which supports neuronal functionality and viability, is, after all, potentially produced in AD-affected neurons, albeit not conventionally but in an ISR-driven and -compatible process. Thus, the present narrative begins with the “omnipotent” Aβ capable of both triggering and driving the disease and ends up with this peptide largely dislodged from its pedestal and retaining its central role in triggering the disease in only one, although prevalent (conventional), category of AD (and driving it in none). Among interesting inferences of the present Perspective is the determination that “sporadic AD” is not sporadic at all (“non-familial” would be a much better designation). The term has fatalistic connotations, implying that the disease can strike at random. This is patently not the case: The conventional disease affects a distinct subpopulation, and the basis for unconventional AD is well understood. Another conclusion is that, unless prevented, the occurrence of conventional AD is inevitable given a sufficiently long lifespan. This Perspective also defines therapeutic directions not to be taken as well as auspicious ways forward. The former category includes ACH-based drugs (those interfering with the proteolytic production of Aβ and/or depleting extracellular Aβ). They are legitimate (albeit inefficient) preventive agents for conventional AD. There is, however, a proverbial snowball’s chance in hell of them being effective in symptomatic AD, lecanemab, donanemab, and any other “…mab” or “…stat” notwithstanding. They comprise Aβ-specific antibodies, inhibitors of beta- and gamma-secretase, and modulators of the latter. In the latter category, among ways to go are the following: (1) Depletion of iAβ, which, if sufficiently “deep”, opens up a tantalizing possibility of once-in-a-lifetime preventive transient treatment for conventional AD and aging-associated cognitive decline, AACD. (2) Composite therapy comprising the degradation of C99/iAβ and concurrent inhibition of the neuronal ISR. A single transient treatment could be sufficient to arrest the progression of conventional AD and prevent its recurrence for life. Multiple recurrent treatments would achieve the same outcome in unconventional AD. Alternatively, the sustained reduction/removal of unconventional neuronal ISR-eliciting stressors through the elimination of their source would convert unconventional AD into conventional one, preventable/treatable by a single transient administration of the composite C99/iAβ depletion/ISR suppression therapy. Efficient and suitable ISR inhibitors are available, and it is explicitly clear where to look for C99/iAβ-specific targeted degradation agents—activators of BACE1 and, especially, BACE2. Directly acting C99/iAβ-specific degradation agents such as proteolysis-targeting chimeras (PROTACs) and molecular-glue degraders (MGDs) are also viable options. (3) A circumscribed shift (either upstream or downstream) of the position of transcription start site (TSS) of the human AβPP gene, or, alternatively, a gene editing-mediated excision or replacement of a small, defined segment of its portion encoding 5′-untranslated region of AβPP mRNA; targeting AβPP RNA with anti-antisense oligonucleotides is another possibility. If properly executed, these RNA-based strategies would not interfere with the protein-coding potential of AβPP mRNA, and each would be capable of both preventing and stopping the AβPP-independent generation of C99 and thus of either preventing AD or arresting the progression of the disease in its conventional and unconventional forms. The paper is interspersed with “validation” sections: every conceptually significant notion is either validated by the existing data or an experimental procedure validating it is proposed.
Full article
(This article belongs to the Special Issue Traumatic Brain Injury/Chronic Traumatic Encephalopathy as Cause of Alzheimer’s Disease: Physics and Molecular Biology in the Genesis of Neurodegeneration?)
Open AccessReview
In Vivo Insights into the Role of Astragaloside IV in Preventing and Treating Civilization Diseases: A Comprehensive Review
by
Katarzyna Stępnik, Agata Jarząb, Rafał Niedźwiadek, Anna Głowniak-Lipa, Kazimierz Głowniak and Wirginia Kukula-Koch
Int. J. Mol. Sci. 2025, 26(9), 4250; https://doi.org/10.3390/ijms26094250 (registering DOI) - 29 Apr 2025
Abstract
Civilization diseases are a growing and global health problem in modern societies. Neurological disorders, cancer, and inflammatory diseases affect a large group of patients around the world. Therefore, it is of utmost importance to search for novel drugs, lifestyle tips, and foods that
[...] Read more.
Civilization diseases are a growing and global health problem in modern societies. Neurological disorders, cancer, and inflammatory diseases affect a large group of patients around the world. Therefore, it is of utmost importance to search for novel drugs, lifestyle tips, and foods that can help restore balance in the living organism, promote the efficiency of the immune system, and provide satisfactory prophylactic measures. Astragaloside IV (ASIV)—a triterpenoid saponin from Astragalus species, one of the world’s most widely used herbs—has been shown to have a variety of biological properties, including anti-inflammatory, antioxidant, antitumor, and neuroprotective effects. In recent years, the number of in vivo studies on this active ingredient in the scientific literature has increased considerably. The aim of this review was therefore to compile the existing knowledge on the use of this compound in the treatment of selected diseases of civilization—cancer, neurological disorders, and inflammatory diseases—in vivo.
Full article
(This article belongs to the Special Issue Plant Metabolites with Pro-cognitive and Neuroprotective Effects)
Open AccessArticle
Big Data-Driven Evolution of a Diagnostic Multiplex IgE-Test: Enhancing Accuracy and Efficacy in Allergy Diagnostics
by
Christian Lupinek, Peter Forstenlechner, Anna Ringauf, Raffaela Campana, Artan Salihu, Martina Aumayr and Irene Mittermann
Int. J. Mol. Sci. 2025, 26(9), 4249; https://doi.org/10.3390/ijms26094249 (registering DOI) - 29 Apr 2025
Abstract
The ALEX2-test (MacroArray Diagnostics, Vienna, Austria) is a diagnostic multiplex IgE-test for the simultaneous detection of IgE to 178 allergens and 117 extracts, in addition to total IgE. Test results from more than 90 countries are stored on a GDPR-compliant cloud
[...] Read more.
The ALEX2-test (MacroArray Diagnostics, Vienna, Austria) is a diagnostic multiplex IgE-test for the simultaneous detection of IgE to 178 allergens and 117 extracts, in addition to total IgE. Test results from more than 90 countries are stored on a GDPR-compliant cloud server for backup, customer support, and continuous postmarket surveillance. To improve the coverage of exposomes on a global scale and to further increase the sensitivity of the test, the allergen panel was updated from ALEX2 to ALEX3. By mid-2023, when ALEX3 was designed, almost 400,000 real-world ALEX2 test results were available. Analysing prevalences and average sIgE-levels of individual allergen preparations, coverage of extracts by components, and co-reactivity of members of the same allergen family provided a rationale for updating the array. In parallel, based on the scientific literature and clinical studies, new allergens were selected. On ALEX3, 218 allergens and 82 extracts will be represented, including 52 new allergens. Allergen preparations with low prevalence and clinical relevance, as well as redundant allergens and extracts, were discontinued. New allergens encompass, e.g., cyclophilins, alpha-gal, and additional markers from respiratory and food allergen sources. Using a large dataset of ALEX2 test results exemplifies the targeted, data-driven improvement of a diagnostic IgE-macroarray.
Full article
(This article belongs to the Special Issue Molecular Understanding of Allergen Exposome)
Open AccessArticle
Ectropis obliqua-Induced Secondary Metabolites Are Regulated by Methyl Jasmonate in a Threshold-Dependent Manner
by
Yongchen Yu, Xiaona Qian, Xiwang Li, Zhichao Chai, Dejiang Ni and Xiaoling Sun
Int. J. Mol. Sci. 2025, 26(9), 4248; https://doi.org/10.3390/ijms26094248 (registering DOI) - 29 Apr 2025
Abstract
The jasmonic acid (JA) signaling pathway has been demonstrated to play a crucial role in plant defense against herbivorous insects. However, the relationship between Ectropis obliqua-induced defensive metabolites and the JA signaling pathway in tea plants remains poorly understood. In this study,
[...] Read more.
The jasmonic acid (JA) signaling pathway has been demonstrated to play a crucial role in plant defense against herbivorous insects. However, the relationship between Ectropis obliqua-induced defensive metabolites and the JA signaling pathway in tea plants remains poorly understood. In this study, we investigated seven key special metabolites, including p-coumaroylputrescine, feruloylputrescine, prunin, naringenin, and three monolignols, to address this knowledge gap. Epicatechin was selected as a positive control based on its well-documented regulation through the JA signaling pathway. Notably, the content of all selected compounds was significantly increased by E. obliqua infestation. Furthermore, exogenous application of high-dose methyl jasmonate (MeJA) induced the accumulation of six of the eight compounds, excluding p-coumaryl alcohol and sinapyl alcohol, whereas low-dose MeJA failed to elicit their accumulation. To confirm the results, we screened two bioactive molecules, D-allose and L-theanine, which significantly increased the endogenous JA levels at low concentrations. Interestingly, neither D-allose nor L-theanine triggered the biosynthesis of these defensive compounds. Additionally, D-allose-treated tea leaves had no significant effect on the performance of E. obliqua larvae. These findings demonstrate that the metabolic accumulation induced by E. obliqua is mediated through a high-threshold JA signaling cascade. This study provides novel insights into the relationship between plant resistance and JA signaling pathway, advancing our understanding of special metabolites mediated plant-insect interactions.
Full article
(This article belongs to the Section Molecular Plant Sciences)
Open AccessArticle
Placental Protein Citrullination Signatures Are Modified in Early- and Late-Onset Fetal Growth Restriction
by
Owen R. Vaughan, Kasia Maksym, Sara Hillman, Rebecca N. Spencer, Mariya Hristova, Anna L. David and Sigrun Lange
Int. J. Mol. Sci. 2025, 26(9), 4247; https://doi.org/10.3390/ijms26094247 (registering DOI) - 29 Apr 2025
Abstract
Fetal growth restriction (FGR) is an obstetric condition most frequently caused by placental dysfunction. It is a major cause of perinatal morbidity with limited treatment options, so identifying the underpinning mechanisms is important. Peptidylarginine deiminases (PADs) are calcium-activated enzymes that mediate post-translational citrullination
[...] Read more.
Fetal growth restriction (FGR) is an obstetric condition most frequently caused by placental dysfunction. It is a major cause of perinatal morbidity with limited treatment options, so identifying the underpinning mechanisms is important. Peptidylarginine deiminases (PADs) are calcium-activated enzymes that mediate post-translational citrullination (deimination) of proteins, through conversion of arginine to citrulline. Protein citrullination leads to irreversible changes in protein structure and function and is implicated in many pathobiological processes. Whether placental protein citrullination occurs in FGR is poorly understood. We assessed protein citrullination and PAD isozyme abundance (PAD1, 2, 3, 4 and 6) in human placental samples from pregnancies complicated by early- and late-onset FGR, compared to appropriate-for-gestational-age (AGA) controls. Proteomic mass spectrometry demonstrated that the placental citrullinome profile changed in both early- and late-onset FGR, with 112 and 345 uniquely citrullinated proteins identified in early- and late-onset samples, respectively. Forty-four proteins were citrullinated only in control AGA placentas. The proteins that were uniquely citrullinated in FGR placentas were enriched for gene ontology (GO) terms related to neurological, developmental, immune and metabolic pathways. A greater number of GO and human phenotype pathways were functionally enriched for citrullinated proteins in late- compared with early-onset FGR. Correspondingly, late-onset but not early-onset FGR was associated with significantly increased placental abundance of PAD2 and citrullinated histone H3, determined by Western blotting. PAD3 was downregulated in early-onset FGR while abundance of PAD 1, 4 and 6 was less altered in FGR. Our findings show that placental protein citrullination is altered in FGR placentas, potentially contributing to the pathobiology of placental dysfunction.
Full article
(This article belongs to the Section Molecular Biology)
Open AccessArticle
Repercussions of the Calpain Cleavage-Related Missense Mutations in the Cytosolic Domains of Human Integrin-β Subunits on the Calpain–Integrin Signaling Axis
by
Reshma V. Kizhakethil, Ashok K. Varma, Sagar H. Barage, Neelmegam Ramesh Kumar, Kayalvizhi Nagarajan, Aruni Wilson Santhosh Kumar and Shashank S. Kamble
Int. J. Mol. Sci. 2025, 26(9), 4246; https://doi.org/10.3390/ijms26094246 (registering DOI) - 29 Apr 2025
Abstract
Calpains, calcium-dependent cytosolic cysteine proteases, perform controlled proteolysis of their substrates for various cellular and physiological activities. In different cancers, missense mutations accumulate in the genes coding for the calpain cleavage sites in various calpain substrates termed as the calpain cleavage-related mutations (CCRMs).
[...] Read more.
Calpains, calcium-dependent cytosolic cysteine proteases, perform controlled proteolysis of their substrates for various cellular and physiological activities. In different cancers, missense mutations accumulate in the genes coding for the calpain cleavage sites in various calpain substrates termed as the calpain cleavage-related mutations (CCRMs). However, the impact of such CCRMs on the calpain–substrate interaction is yet to be explored. This study focuses on the interaction of wild-type and mutant β-integrins with calpain-1 and 2 in uterine corpus endometrial carcinoma (UCEC). A total of 48 calpain substrates with 176 CCRMs were retrieved from different datasets and shortlisted on the basis of their involvement in cancer pathways. Finally, three calpain substrates, ITGB1, ITGB3, and ITGB7, were selected to assess the structural changes due to CCRMs. These CCRMs were observed towards the C-terminal of the cytoplasmic domain within the calpain cleavage site. The wild-type and mutant proteins were docked with calpain-1 and 2, followed by molecular simulation. The interaction between mutant substrates and calpains showcased variations compared to their respective wild-type counterparts. This may be attributed to mutations in the calpain cleavage sites, highlighting the importance of the cytoplasmic domain of β-integrins in the interactions with calpains and subsequent cellular signaling. Highlights: 1. Calpain cleavage-related mutations (CCRMs) can alter cellular signaling. 2. CCRMs impact the structure of C-domains of human integrin-β subunits. 3. Altered structure influences the cleavability of human integrin-β subunits by human calpains. 4. Altered cleavability impacts the cell signaling mediated through calpain–integrin-β axis. 5. Presence of CCRMS may influence the progression of uterine corpus endometrial carcinoma (UCEC).
Full article
(This article belongs to the Special Issue Research on Gene Mutations in Cancer and Chronic Diseases)
►▼
Show Figures

Figure 1
Open AccessArticle
CD274 (PD-L1) Polymorphisms as Predictors of Efficacy in First-Line Platinum-Based Chemotherapy for Extensive-Stage Small Cell Lung Cancer
by
Andrés Barba, Laura López-Vilaró, Malena Ferre, Sergio Martinez-Recio, Margarita Majem, Ivana Sullivan and Juliana Salazar
Int. J. Mol. Sci. 2025, 26(9), 4245; https://doi.org/10.3390/ijms26094245 (registering DOI) - 29 Apr 2025
Abstract
The cornerstone of first-line treatment in extensive-stage small cell lung cancer (ES-SCLC) is platinum- and etoposide-based chemotherapy. Platinum compounds could immunomodulate the tumor microenvironment in addition to their cytotoxic effect. Genetic variation in immune checkpoint (IC) pathways may predict chemotherapy efficacy. Polymorphisms in
[...] Read more.
The cornerstone of first-line treatment in extensive-stage small cell lung cancer (ES-SCLC) is platinum- and etoposide-based chemotherapy. Platinum compounds could immunomodulate the tumor microenvironment in addition to their cytotoxic effect. Genetic variation in immune checkpoint (IC) pathways may predict chemotherapy efficacy. Polymorphisms in the IC genes were determined, and their association with survival was analyzed in 78 patients with ES-SCLC treated with chemotherapy. PD-L1 protein expression in tumor tissue was determined. Three variants in CD274 were associated with better median progression-free survival (mPFS): rs2297136 (hazard ratio [HR] 0.52, 95% CI 0.29–0.93; p = 0.03), rs2282055 (HR 0.23, 95% CI 0.09–0.64; p = 0.005), and rs822336 (HR 0.41, 95% CI 0.23–0.73; p = 0.002). CTLA4 rs231775 was also associated with mPFS (HR 0.30, 95% CI 0.14–0.63; p = 0.002). The variants CD274 rs2297136 and CD274 rs822336 were associated with platinum sensitivity (odds ratio [OR] 0.13, 95% CI 0.02–0.70; p = 0.02, and OR 0.08, 95% CI 0.01–0.46; p = 0.005, respectively). CD274 rs2297136 was also associated with better overall survival (p = 0.02), but not after adjustment for covariates. No association was found between CD274 germline variants and PD-L1 tumor expression. Our results suggest that CD274 and CTLA4 variants may be predictive biomarkers for platinum plus etoposide treatment in ES-SCLC.
Full article
(This article belongs to the Special Issue Small Cell Lung Cancer Entering the Sphere of Personalized Treatment)
Open AccessArticle
Exosomal microRNA from Plasma in Patients with Pseudoexfoliation Glaucoma of Korea
by
Hyo Jung An, Dae Hyun Song, Changwon Kee and Hyun-kyung Cho
Int. J. Mol. Sci. 2025, 26(9), 4244; https://doi.org/10.3390/ijms26094244 - 29 Apr 2025
Abstract
This study aimed to determine the microRNA (miRNA) profile extracted from exosomes in plasma samples in pseudoexfoliation (PEX) glaucoma patients compared to controls. A blood sample (10 mL) was obtained after acquiring written informed consent. Exosome was extracted from each plasma sample using
[...] Read more.
This study aimed to determine the microRNA (miRNA) profile extracted from exosomes in plasma samples in pseudoexfoliation (PEX) glaucoma patients compared to controls. A blood sample (10 mL) was obtained after acquiring written informed consent. Exosome was extracted from each plasma sample using an Exoquick-TC kit. RNA sequencing was performed for each exosome sample. A bioinformatics study was conducted for miRNA-related pathways and targets. A total of 14 Korean subjects (7 with PEX glaucoma; 7 age-matched controls) were involved in the final study. In exosomes of PEX glaucoma participants, 330 mature miRNAs were detected. Among these, three miRNAs were significantly upregulated, including hsa-miR-92b-5p (fold change: 24.68), hsa-miR-744-5p (fold change: 2.49), and hsa-miR-148b-3p (fold change: 3.96). Sixty-six miRNAs were significantly downregulated in PEX glaucoma patients compared to the controls (all p < 0.05). These significantly altered miRNAs (both upregulated and downregulated) were associated with the gene ontology (GO) category of neurogenesis (9.41%), which accounted for the largest proportion. The expression of exosomal microRNAs in plasma was significantly different between PEX glaucoma patients and the controls. This suggests their possible roles in the pathogenic mechanism and a good diagnostic marker for PEX glaucoma.
Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Open AccessArticle
Paramutation-like Behavior of Genic piRNA-Producing Loci in Drosophila virilis
by
Alina V. Bespalova, Dina A. Kulikova, Elena S. Zelentsova, Alexander P. Rezvykh, Iuliia O. Guseva, Ana P. Dorador, Mikhail B. Evgen’ev and Sergei Y. Funikov
Int. J. Mol. Sci. 2025, 26(9), 4243; https://doi.org/10.3390/ijms26094243 (registering DOI) - 29 Apr 2025
Abstract
Piwi-interacting RNAs (piRNAs) play a crucial role in silencing transposable elements (TEs) in the germ cells of Metazoa by acting as sequence-specific guides. Originating from distinct genomic loci, called piRNA clusters, piRNA can trigger an epigenetic conversion of TE insertions into piRNA clusters
[...] Read more.
Piwi-interacting RNAs (piRNAs) play a crucial role in silencing transposable elements (TEs) in the germ cells of Metazoa by acting as sequence-specific guides. Originating from distinct genomic loci, called piRNA clusters, piRNA can trigger an epigenetic conversion of TE insertions into piRNA clusters by means of a paramutation-like process. However, the variability in piRNA clusters’ capacity to induce such conversions remains poorly understood. Here, we investigated two Drosophila virilis strains with differing capacities to produce piRNAs from the subtelomeric RhoGEF3 and Adar gene loci. We found that active piRNA generation correlates with high levels of the heterochromatic mark histone 3 lysine 9 trimethylation (H3K9me3) over genomic regions that give rise to piRNAs. Importantly, the maternal transmission of piRNAs drives their production in the progeny, even from homologous loci previously inactive in piRNA biogenesis. The RhoGEF3 locus, once epigenetically converted, maintained enhanced piRNA production in subsequent generations lacking the original allele carrying the active piRNA cluster. In contrast, piRNA expression from the converted Adar locus was lost in offspring lacking the inducer allele. The present findings suggest that the paramutation-like behavior of piRNA clusters may be influenced not only by piRNAs but also by structural features and the chromatin environment in the proximity to telomeres, providing new insights into the epigenetic regulation of the Drosophila genome.
Full article
(This article belongs to the Section Molecular Genetics and Genomics)
Open AccessReview
Evolution in Bone Tissue Regeneration: From Grafts to Innovative Biomaterials
by
Domingo Cesar Carrascal-Hernández, Juan Pablo Martínez-Cano, Juan David Rodríguez Macías and Carlos David Grande-Tovar
Int. J. Mol. Sci. 2025, 26(9), 4242; https://doi.org/10.3390/ijms26094242 - 29 Apr 2025
Abstract
Bone defects caused by various traumas and diseases such as osteoporosis, which affects bone density, and osteosarcoma, which affects the integrity of bone structure, are now well known. Given this situation, several innovative research projects have been reported to improve orthopedic methods and
[...] Read more.
Bone defects caused by various traumas and diseases such as osteoporosis, which affects bone density, and osteosarcoma, which affects the integrity of bone structure, are now well known. Given this situation, several innovative research projects have been reported to improve orthopedic methods and technologies that positively contribute to the regeneration of affected bone tissue, representing a significant advance in regenerative medicine. This review article comprehensively analyzes the transition from existing methods and technologies for implants and bone tissue regeneration to innovative biomaterials. These biomaterials have been of great interest in the last decade due to their physicochemical characteristics, which allow them to overcome the most common limitations of traditional grafting methods, such as the availability of biomaterials and the risk of rejection after their application in regenerative medicine. This could be achieved through an exhaustive study of the applications and properties of various materials with potential applications in regenerative medicine, such as using magnetic nanoparticles and hydrogels sensitive to external stimuli, including pH and temperature. In this regard, this review article describes the most relevant compounds used in bone tissue regeneration, promoting the integration of these biomaterials with the affected area’s bone structure, thereby allowing for regeneration and preventing amputation. Additionally, the types of interactions between biomaterials and mesenchymal stem cells and their effects on bone tissue are discussed, which is critical for developing biomaterials with optimal regenerative properties. Furthermore, the mechanisms of action of the various biomaterials that enhance osteoconduction and osteoinduction, ensuring the success of orthopedic therapies, are analyzed. This enables the treatment of bone defects tailored to each patient’s condition, thereby avoiding limb amputation. Consequently, a promising future for regenerative medicine is emerging, with various therapies that could revolutionize the management of bone defects, offering more efficient and safer solutions.
Full article
(This article belongs to the Special Issue Bone Tissue Engineering: Opportunities and Challenges)
Open AccessArticle
The Genetic Elements of the Obesity Paradox in Atherosclerosis Identified in an Intercross Between Hyperlipidemic Mouse Strains
by
Mei-Hua Chen, Bilhan Chagari, Ashley M. Abramson, Lisa J. Shi, Jiang He and Weibin Shi
Int. J. Mol. Sci. 2025, 26(9), 4241; https://doi.org/10.3390/ijms26094241 - 29 Apr 2025
Abstract
Overweight and obese individuals show lower mortality rates or better prognoses than those of normal weight in a variety of diseases, a phenomenon called the “obesity paradox”. An inverse association of adiposity with atherosclerosis has been observed in both humans and mice. To
[...] Read more.
Overweight and obese individuals show lower mortality rates or better prognoses than those of normal weight in a variety of diseases, a phenomenon called the “obesity paradox”. An inverse association of adiposity with atherosclerosis has been observed in both humans and mice. To dissect phenotypic and genetic connections between the traits, 154 female and 145 male F2 mice were generated from an intercross between BALB/cJ and LP/J apolipoprotein E-deficient mice and fed a Western diet for 12 weeks. Atherosclerotic lesion size in the aortic root, body weight, plasma lipids, and glucose were measured, and genotyping was performed on miniMUGA SNP arrays. Quantitative trait locus (QTL) analyses on all F2 mice with sex as a covariate revealed four significant QTLs on chromosomes (Chr) 3, 6, 13, and 15 for atherosclerosis and three significant QTLs on Chr2, 7, and 15 for body weight. Chr15 QTL for atherosclerosis overlapped with one for body weight near 36 Mb. After adjusting for variation in body weight, Chr15 atherosclerosis QTL was downgraded from significant to suggestive linkage. Body weight was inversely correlated with atherosclerotic lesion sizes and accounted for more variance than a single other risk factor for atherosclerosis among F2 mice. Analysis of public data collected from two backcross cohorts revealed strong correlations between body weight and fat mass in adult mice (r ≥ 0.93; p ≤ 1.6 × 10−136). Thus, the obesity paradox in atherosclerosis is partially attributable to shared genetic components that have an opposite effect on adiposity and atherosclerosis.
Full article
(This article belongs to the Special Issue Molecular Mechanisms Linking Obesity to Atherosclerosis Pathogenesis)
Open AccessReview
Crosstalk Between Bile Acids and Intestinal Epithelium: Multidimensional Roles of Farnesoid X Receptor and Takeda G Protein Receptor 5
by
Xiulian Lin, Li Xia, Yuanjiao Zhou, Jingchen Xie, Qinhui Tuo, Limei Lin and Duanfang Liao
Int. J. Mol. Sci. 2025, 26(9), 4240; https://doi.org/10.3390/ijms26094240 (registering DOI) - 29 Apr 2025
Abstract
Bile acids and their corresponding intestinal epithelial receptors, the farnesoid X receptor (FXR), the G protein-coupled bile acid receptor (TGR5), play crucial roles in the physiological and pathological processes of intestinal epithelial cells. These acids and receptors are involved in the regulation of
[...] Read more.
Bile acids and their corresponding intestinal epithelial receptors, the farnesoid X receptor (FXR), the G protein-coupled bile acid receptor (TGR5), play crucial roles in the physiological and pathological processes of intestinal epithelial cells. These acids and receptors are involved in the regulation of intestinal absorption, signal transduction, cellular proliferation and repair, cellular senescence, energy metabolism, and the modulation of gut microbiota. A comprehensive literature search was conducted using PubMed, employing keywords such as bile acid, bile acid receptor, FXR (nr1h4), TGR5 (gpbar1), intestinal epithelial cells, proliferation, differentiation, senescence, energy metabolism, gut microbiota, inflammatory bowel disease (IBD), colorectal cancer (CRC), and irritable bowel syndrome (IBS), with a focus on publications available in English. This review examines the diverse effects of bile acid signaling and bile receptor pathways on the proliferation, differentiation, senescence, and energy metabolism of intestinal epithelial cells. Additionally, it explores the interactions between bile acids, their receptors, and the microbiota, as well as the implications of these interactions for host health, particularly in relation to prevalent intestinal diseases. Finally, the review highlights the importance of developing highly specific ligands for FXR and TGR5 receptors in the context of metabolic and intestinal disorders.
Full article
(This article belongs to the Special Issue Advances in Bioactive Molecules)
►▼
Show Figures

Graphical abstract
Open AccessArticle
Abnormally Increased Prolactin Levels in Women with Polycystic Ovarian Syndrome Are Associated with Risk of Obesity, Insulin Resistance and Prediabetes
by
Vesselina Yanachkova and Teodora Stankova
Int. J. Mol. Sci. 2025, 26(9), 4239; https://doi.org/10.3390/ijms26094239 - 29 Apr 2025
Abstract
Polycystic ovarian syndrome (PCOS) is a prevalent endocrine condition in women of reproductive age, characterized also by insulin resistance, affecting both obese and non-obese individuals. Hyperprolactinemia in patients with PCOS may additionally aggravate the decline in insulin sensitivity, attributable to prolactin lipogenic effects
[...] Read more.
Polycystic ovarian syndrome (PCOS) is a prevalent endocrine condition in women of reproductive age, characterized also by insulin resistance, affecting both obese and non-obese individuals. Hyperprolactinemia in patients with PCOS may additionally aggravate the decline in insulin sensitivity, attributable to prolactin lipogenic effects and influence on metabolic profile. Therefore, this study aimed to investigate the serum levels of prolactin in women with PCOS and their associations with obesity, insulin resistance and prediabetes. A retrospective monocentric study was performed using the electronic database of 157 women diagnosed with PCOS. Serum prolactin, BMI, complete glucose-insulin profile and insulin resistance indices following OGTT were determined. The women with hyperprolactinemia (40.8%) had significantly higher BMI (p = 0.007), fasting glucose (p = 0.003), insulin levels (p < 0.001) and HOMA-IR (p < 0.001). The women with PCOS categorized as overweight/obese (47.1%), insulin resistant (68.8%), having impaired fasting glycaemia (28.7%) and prediabetes (36.3%) showed significantly higher levels of prolactin compared to the respective counterparts. Consequently, higher prolactin levels were significantly associated with an elevated risk of development of overweight/obesity (OR 2.59; 95% CI: 1.34–4.97, p = 0.004), insulin resistance (OR 3.33; 95% CI: 1.54–7.19, p = 0.002) and prediabetes (OR 1.98; 95% CI: 1.02–3.85, p = 0.043) in women with PCOS. Our results suggest that hyperprolactinemia might be a pathophysiological link between obesity, insulin resistance, and carbohydrate metabolism impairments in patients with PCOS. Increased prolactin levels may serve as an additional indicator of insulin resistance and even further exacerbate it in women with PCOS.
Full article
(This article belongs to the Special Issue Molecular Research on Reproductive Physiology and Endocrinology)
►▼
Show Figures

Figure 1
Open AccessArticle
Innovative Amber-Based Composite—From Mechanochemical Synthesis and Physicochemical Characterization to Application in Cosmetics
by
Małgorzata Wiśniewska, Victoria Paientko, Iwona Ostolska, Karina Tokarska, Natalia Kurinna, Vita Vedmedenko, Olha Konshyna, Volodymyr Gun’ko and Piotr Nowicki
Int. J. Mol. Sci. 2025, 26(9), 4238; https://doi.org/10.3390/ijms26094238 - 29 Apr 2025
Abstract
New ways of ensuring sustainable development in various areas of life are being intensively researched. One of the key priorities is to maximize the use of invaluable natural ingredients in cosmetic products while minimizing the negative impact on the environment. In this study,
[...] Read more.
New ways of ensuring sustainable development in various areas of life are being intensively researched. One of the key priorities is to maximize the use of invaluable natural ingredients in cosmetic products while minimizing the negative impact on the environment. In this study, a three-component natural composite based on amber, diatomite, and PhytokeratinTM (hydrolyzed plant protein) was developed using mechanochemical synthesis. The goal was to maximize the release of biologically active substances, such as succinic acid and PhytokeratinTM, in aqueous solution. The physicochemical properties of the materials were characterized using Scanning Electron Microscopy (SEM), thermogravimetric (TG) and differential thermogravimetric (DTG) analysis, Fourier Transform Infrared (FTIR) spectroscopy, and Ultraviolet–Visible (UV-Vis) spectrophotometry. Additionally, Density Functional Theory (DFT) was used to perform quantum chemical calculations and characterize molecular interactions in the composite. The optimized composite demonstrated favorable release characteristics and structural properties, confirming its suitability for cosmetic applications. DFT calculations revealed the potential molecular-level interactions between the organic components, indicating the stability and functional integration of the composite. The resulting innovative composite was successfully incorporated into eco-friendly cosmetic formulations, including a solid shampoo bar and a nail conditioner.
Full article
(This article belongs to the Special Issue Organic/Inorganic Nanocomposites on the Basis of 'Three Pillars' (Organic Compounds, Metal Nanoparticles, and Carbon Nanomaterials))
►▼
Show Figures

Graphical abstract
Open AccessCase Report
A Novel Homozygous 9385 bp Deletion in the FERMT1 (KIND1) Gene in a Malaysian Family with Kindler Epidermolysis bullosa and a Review of Large Deletions
by
Alfred Klausegger, Fabian Leditzky, Susanne Krämer, Francis Palisson, María Joao Yubero, Sebastián Véliz, Mark Jean Aan Koh, Ene-Choo Tan, Martin Laimer, Johann Wolfgang Bauer and Ignacia Fuentes
Int. J. Mol. Sci. 2025, 26(9), 4237; https://doi.org/10.3390/ijms26094237 - 29 Apr 2025
Abstract
Kindler Epidermolysis bullosa (KEB; OMIM 173650) is a rare autosomal recessive genodermatosis characterized by bullous poikiloderma and photosensitivity. Additional presentations include blistering, poor wound healing, skin atrophy, and increased risk of skin cancer. Most cases of KEB result from aberrations in the FERMT1
[...] Read more.
Kindler Epidermolysis bullosa (KEB; OMIM 173650) is a rare autosomal recessive genodermatosis characterized by bullous poikiloderma and photosensitivity. Additional presentations include blistering, poor wound healing, skin atrophy, and increased risk of skin cancer. Most cases of KEB result from aberrations in the FERMT1 (Fermitin family member 1) gene encoding kindlin-1 and include nonsense, frameshift, splicing, and missense variants. Large deletion variants have been reported in nine cases to date. Most variants are predicted to lead to premature termination of translation and to loss of kindlin-1 function. In this study, we report on a 33-year-old male patient who presented with typical clinical manifestations of KEB. As routine molecular testing failed to obtain a diagnosis, Next Generation Sequencing (NGS) of an Epidermolysis Bullosa (EB)-specific panel was carried out followed by the determination of the deletion breakpoints and verification at the mRNA and protein levels. This approach revealed a new large homozygous deletion of ~9.4 kb in the FERMT1 gene involving exons 7 to 9. Finally, we performed a literature review on large FERMT1 deletions. The deletion is predicted to skip exons 7 to 9 within the mRNA, which results in a frameshift. The patient’s phenotype is likely caused by the resulting truncated and non-functioning protein. Our report further enriches the spectrum of FERMT1 gene variants to improve genotype–phenotype correlations.
Full article
(This article belongs to the Special Issue Genetic Mutations in Health and Disease)
►▼
Show Figures

Graphical abstract
Open AccessArticle
Proteomic Profiling of Hu Sheep Placental Development Across Gestational Stages Reveals Stage-Specific Regulatory Networks
by
Zhibo Wang, Jiahe Guo, Tianning Dong, Yaxu Liang, Zhipeng Liu, Feng Wang and Yanli Zhang
Int. J. Mol. Sci. 2025, 26(9), 4236; https://doi.org/10.3390/ijms26094236 - 29 Apr 2025
Abstract
Placental development plays a pivotal role in ensuring successful pregnancy outcomes, yet its molecular regulatory mechanisms in sheep remain poorly characterized. This study aimed to systematically investigate stage-specific proteomic dynamics and functional adaptations in ovine placental tissues across gestation to elucidate molecular drivers
[...] Read more.
Placental development plays a pivotal role in ensuring successful pregnancy outcomes, yet its molecular regulatory mechanisms in sheep remain poorly characterized. This study aimed to systematically investigate stage-specific proteomic dynamics and functional adaptations in ovine placental tissues across gestation to elucidate molecular drivers of placental maturation. Using data-independent acquisition proteomics, we identified 7774 proteins in Hu sheep placental tissues at gestational days 50, 80, and 120. Comparative analysis revealed 1450, 1026, and 1964 differentially expressed proteins (DEPs) in the 50 d vs. 80 d, 80 d vs. 120 d, and 50 d vs. 120 d comparisons, respectively. DEPs were functionally enriched in biological processes including cell proliferation, apoptosis, angiogenesis, nutrient transport, and steroid synthesis, with prominent involvement of the PI3K-Akt, MAPK, and estrogen signaling pathways. Protein interaction networks identified SRC, MAP3K1, KRAS, and TJP1 as central regulators exhibiting dynamic expression patterns across gestation. Temporal expression trends showed progressive upregulation of tight junction, immune response, and glucose metabolism proteins, contrasting with downregulation of endoplasmic reticulum protein processing and proteasome components. Validation experiments confirmed elevated proliferation/transport gene expression at 80 d versus 50 d, followed by increased apoptosis/transport genes and decreased proliferation markers at 120 d. This comprehensive proteomic profiling reveals stage-specific regulatory networks governing placental development in sheep, highlighting coordinated shifts in proliferative, metabolic, and structural remodeling processes. These findings advance our understanding of placental adaptation mechanisms and provide valuable insights for improving reproductive management in livestock species.
Full article
(This article belongs to the Section Molecular Biology)
►▼
Show Figures

Figure 1
Open AccessBrief Report
Anti-Influenza Activity of 6BIGOE: Improved Pharmacological Profile After Encapsulation in PLGA Nanoparticles
by
Josefine Schroeder, Jan Westhoff, Ivan Vilotijević, Oliver Werz, Stephanie Hoeppener, Bettina Löffler, Dagmar Fischer and Christina Ehrhardt
Int. J. Mol. Sci. 2025, 26(9), 4235; https://doi.org/10.3390/ijms26094235 - 29 Apr 2025
Abstract
Influenza A virus (IAV) infections continue to threaten public health. Current strategies, such as vaccines and antiviral drugs, are limited due to their time-consuming development and drug-resistant strains. Therefore, new effective treatments are needed. Here, virus-supportive cellular factors are promising drug targets, and
[...] Read more.
Influenza A virus (IAV) infections continue to threaten public health. Current strategies, such as vaccines and antiviral drugs, are limited due to their time-consuming development and drug-resistant strains. Therefore, new effective treatments are needed. Here, virus-supportive cellular factors are promising drug targets, and the encapsulation of candidate substances in poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) is intended to improve their bioavailability. This study investigates the potential of the indirubin derivative 6-bromoindirubin-3′-glycerol-oxime ether (6BIGOE), a glycogen synthase kinase 3 (GSK-3)β inhibitor, for its potential to regulate IAV replication in vitro. The effects of 6BIGOE-loaded PLGA NPs on cell metabolism were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays in A549 and Calu-3 cells. Viral replication and spread were monitored in various IAV-infected cell lines in the absence and presence of free and 6BIGOE-loaded PLGA NPs via plaque assays and Western blot analysis. The encapsulation of 6BIGOE in PLGA NPs resulted in reduced negative side effects on cell viability while maintaining antiviral efficacy. Both encapsulated and free 6BIGOE exhibited antiviral activity, potentially through GSK-3β inhibition and the disruption of key signaling pathways required for viral replication. The data indicate 6BIGOE, particularly after encapsulation in NPs, as a potential candidate for further investigation and development as an antiviral agent to treat IAV infections.
Full article
(This article belongs to the Section Molecular Nanoscience)
Open AccessArticle
TFProtBert: Detection of Transcription Factors Binding to Methylated DNA Using ProtBert Latent Space Representation
by
Saima Gaffar, Kil To Chong and Hilal Tayara
Int. J. Mol. Sci. 2025, 26(9), 4234; https://doi.org/10.3390/ijms26094234 - 29 Apr 2025
Abstract
Transcription factors (TFs) are fundamental regulators of gene expression and perform diverse functions in cellular processes. The management of 3-dimensional (3D) genome conformation and gene expression relies primarily on TFs. TFs are crucial regulators of gene expression, performing various roles in biological processes.
[...] Read more.
Transcription factors (TFs) are fundamental regulators of gene expression and perform diverse functions in cellular processes. The management of 3-dimensional (3D) genome conformation and gene expression relies primarily on TFs. TFs are crucial regulators of gene expression, performing various roles in biological processes. They attract transcriptional machinery to the enhancers or promoters of specific genes, thereby activating or inhibiting transcription. Identifying these TFs is a significant step towards understanding cellular gene expression mechanisms. Due to the time-consuming and labor-intensive nature of experimental methods, the development of computational models is essential. In this work, we introduced a two-layer prediction framework based on a support vector machine (SVM) using the latent space representation of a protein language model, ProtBert. The first layer of the method reliably predicts and identifies transcription factors (TFs), and in the second layer, the proposed method predicts and identifies transcription factors that prefer binding to methylated deoxyribonucleic acid (TFPMs). In addition, we also tested the proposed method on an imbalanced database. In detecting TFs and TFPMs, the proposed model consistently outperformed state-of-the-art approaches, as demonstrated by performance comparisons via empirical cross-validation analysis and independent tests.
Full article
(This article belongs to the Special Issue Applications of Machine Learning in Bioinformatics and Biomedicine)

Journal Menu
► ▼ Journal Menu-
- IJMS Home
- Aims & Scope
- Editorial Board
- Reviewer Board
- Topical Advisory Panel
- Instructions for Authors
- Special Issues
- Topics
- Sections & Collections
- Article Processing Charge
- Indexing & Archiving
- Most Cited & Viewed
- Journal Statistics
- Journal History
- Journal Awards
- Society Collaborations
- Conferences
- Editorial Office
Journal Browser
► ▼ Journal Browser-
arrow_forward_ios
Forthcoming issue
arrow_forward_ios Current issue - Vol. 26 (2025)
- Vol. 25 (2024)
- Vol. 24 (2023)
- Vol. 23 (2022)
- Vol. 22 (2021)
- Vol. 21 (2020)
- Vol. 20 (2019)
- Vol. 19 (2018)
- Vol. 18 (2017)
- Vol. 17 (2016)
- Vol. 16 (2015)
- Vol. 15 (2014)
- Vol. 14 (2013)
- Vol. 13 (2012)
- Vol. 12 (2011)
- Vol. 11 (2010)
- Vol. 10 (2009)
- Vol. 9 (2008)
- Vol. 8 (2007)
- Vol. 7 (2006)
- Vol. 6 (2005)
- Vol. 5 (2004)
- Vol. 4 (2003)
- Vol. 3 (2002)
- Vol. 2 (2001)
- Vol. 1 (2000)
Highly Accessed Articles
Latest Books
E-Mail Alert
News
Topics
Topic in
BioChem, Biomedicines, Biomolecules, IJMS, Metabolites, Molecules
Natural Products in Prevention and Therapy of Metabolic Syndrome
Topic Editors: Jianbo Wan, Ligen LinDeadline: 30 April 2025
Topic in
Biomedicines, Brain Sciences, CIMB, Diagnostics, IJMS, IJTM
Autism: Molecular Bases, Diagnosis and Therapies, 2nd Volume
Topic Editors: Lello Zolla, Kunio YuiDeadline: 31 May 2025
Topic in
Biomolecules, IJMS, Molecules, Pharmaceutics
Advances in Diagnostics, Brain Delivery Systems and Therapeutics of Neurodegenerative Disease
Topic Editors: Ashok Iyaswamy, Chuanbin Yang, Abhimanyu ThakurDeadline: 11 June 2025
Topic in
Chemistry, Foods, IJMS, Molecules, Separations
Recent Trends and Advances in Food Authentication and Traceability
Topic Editors: Michael Kontominas, Anastasia BadekaDeadline: 30 June 2025

Conferences
Special Issues
Special Issue in
IJMS
Antibodies in Cancer Therapy
Guest Editor: Yasushi AkahoriDeadline: 30 April 2025
Special Issue in
IJMS
Biological Hallmarks and Therapeutic Strategies in Cancer
Guest Editor: Ramesh KumarDeadline: 30 April 2025
Special Issue in
IJMS
Application of Fluorescent Probes in Visualization and Intervention Processes in Pathology
Guest Editor: Kang-Nan WangDeadline: 30 April 2025
Special Issue in
IJMS
Molecular Research of Tropical Fruit (2nd Edition)
Guest Editor: Yonghua QinDeadline: 30 April 2025
Topical Collections
Topical Collection in
IJMS
Feature Papers in Molecular Toxicology
Collection Editor: Guido R.M.M. Haenen
Topical Collection in
IJMS
Feature Paper Collection in Molecular Endocrinology and Metabolism
Collection Editor: José L. Quiles
Topical Collection in
IJMS
Bioactive Natural Compounds for Therapeutics and Nutraceutical Applications
Collection Editors: Sonia A.O. Santos, Armando J. D. Silvestre, Raphael Grougnet, Vessela Balabanova
Topical Collection in
IJMS
30th Anniversary of IJMS: Updates and Advances in Biochemistry
Collection Editor: Claudiu T. Supuran