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Metabolic Regulation of Ferroptosis in Breast Cancer -
Reactive Oxygen Species Across Death Pathways: Gatekeepers of Apoptosis, Ferroptosis, Pyroptosis, Paraptosis, and Beyond -
Fusobacterium Nucleatum in Colorectal Cancer: Relationship Among Immune Modulation, Potential Biomarkers and Therapeutic Implications -
Chronic Stress and Autoimmunity: The Role of HPA Axis and Cortisol Dysregulation -
Astatine-211-Labeled Therapy Targeting Amino Acid Transporters: Overcoming Drug Resistance in Non-Small Cell Lung Cancer
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 published semimonthly online by MDPI. The 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 17.8 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 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
Functional Food Potential of White Tea from East Black Sea Region: Targeting GREM1 Expression and Metabolic Dysregulation in Obesity
Int. J. Mol. Sci. 2026, 27(2), 929; https://doi.org/10.3390/ijms27020929 (registering DOI) - 16 Jan 2026
Abstract
Obesity is a major global health concern, being associated with insulin resistance and multiple metabolic disorders. Gremlin 1 (GREM1), a bone morphogenetic protein (BMP) antagonist, is increasingly recognized as a key regulator of adipose tissue dysfunction and impaired thermogenesis in obesity. Orlistat, a
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Obesity is a major global health concern, being associated with insulin resistance and multiple metabolic disorders. Gremlin 1 (GREM1), a bone morphogenetic protein (BMP) antagonist, is increasingly recognized as a key regulator of adipose tissue dysfunction and impaired thermogenesis in obesity. Orlistat, a lipase inhibitor that reduces dietary fat absorption, is one of the most commonly used pharmacological agents for obesity management. White tea has demonstrated antioxidant and anti-obesity properties in experimental models. The aim of this study was to evaluate the effects of white tea on metabolic parameters (HOMA-IR, BMP4, Gremlin1) and GREM1 expression in rats made obese by a high-fat diet (HFD). A total of 40 male Sprague-Dawley rats were randomized into five groups: a standard diet group (STD); a high-fat diet group (HFD); an HFD + orlistat group (ORL); an HFD + 50 mg/kg white tea group (WT50); and an HFD + 150 mg/kg white tea group (WT150). Obesity was induced by feeding the rats a 45% high-fat diet for 3 weeks. Serum insulin, glucose and HOMA-IR levels were measured. Levels of GREM1 and BMP4 in serum and retroperitoneal adipose tissue were assessed. White tea supplementation significantly reduced weight gain and HOMA-IR compared to the HFD group. GREM1 mRNA expression in visceral adipose tissue decreased markedly in the WT50 and WT150 groups (p = 0.002 and p = 0.017, respectively). Serum GREM1 levels were significantly lower in the white tea-treated groups than in the HFD group (p = 0.011). Tissue BMP4 levels were only significantly reduced in the WT50 group (p = 0.005), indicating a non-linear dose–response pattern. There was a negative correlation between serum BMP4 levels and weight gain (rho = –0.440, p = 0.015). White tea was associated with improvements in metabolic parameters in an HFD-induced obesity model. These observations suggest a potential association between white tea bioactives and adipose tissue-related molecular pathways implicated in obesity. Given the short intervention duration and the exploratory design of this animal study, the findings should be interpreted with caution.
Full article
(This article belongs to the Special Issue Bioactive Compounds from Foods Against Diseases)
Open AccessReview
The Glymphatic–Immune Axis in Glioblastoma: Mechanistic Insights and Translational Opportunities
by
Joaquin Fiallo Arroyo and Jose E. Leon-Rojas
Int. J. Mol. Sci. 2026, 27(2), 928; https://doi.org/10.3390/ijms27020928 (registering DOI) - 16 Jan 2026
Abstract
Glioblastoma (GBM) remains one of the most treatment-resistant human malignancies, largely due to the interplay between disrupted fluid dynamics, immune evasion, and the structural complexity of the tumor microenvironment; in addition to these, treatment resistance is also driven by intratumoral heterogeneity, glioma stem
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Glioblastoma (GBM) remains one of the most treatment-resistant human malignancies, largely due to the interplay between disrupted fluid dynamics, immune evasion, and the structural complexity of the tumor microenvironment; in addition to these, treatment resistance is also driven by intratumoral heterogeneity, glioma stem cell persistence, hypoxia-induced metabolic and epigenetic plasticity, adaptive oncogenic signaling, and profound immunosuppression within the tumor microenvironment. Emerging evidence shows that dysfunction of the glymphatic system, mislocalization of aquaporin-4, and increased intracranial pressure compromise cerebrospinal fluid–interstitial fluid exchange and impair antigen drainage to meningeal lymphatics, thereby weakening immunosurveillance. GBM simultaneously remodels the blood–brain barrier into a heterogeneous and permeable blood–tumor barrier that restricts uniform drug penetration yet enables tumor progression. These alterations intersect with profound immunosuppression mediated by pericytes, tumor-associated macrophages, and hypoxic niches. Advances in imaging, including DCE-MRI, DTI-ALPS, CSF-tracing PET, and elastography, now allow in vivo characterization of glymphatic function and interstitial flow. Therapeutic strategies targeting the fluid-immune interface are rapidly expanding, including convection-enhanced delivery, intrathecal and intranasal approaches, focused ultrasound, nanoparticle systems, and lymphatic-modulating immunotherapies such as VEGF-C and STING agonists. Integrating barrier modulation with immunotherapy and nanomedicine holds promise for overcoming treatment resistance. Our review synthesizes the mechanistic, microenvironmental, and translational advances that position the glymphatic–immune axis as a new frontier in glioblastoma research.
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(This article belongs to the Special Issue Updates and Advances in the Field of Glioblastomas: Mechanisms, Microenvironment and Treatments)
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Open AccessReview
Silver Nanoparticles in Antibacterial Research: Mechanisms, Applications, and Emerging Perspectives
by
Hasan Karataş, Furkan Eker, Emir Akdaşçi, Mikhael Bechelany and Sercan Karav
Int. J. Mol. Sci. 2026, 27(2), 927; https://doi.org/10.3390/ijms27020927 (registering DOI) - 16 Jan 2026
Abstract
Silver nanoparticles (AgNPs) possess distinct physicochemical characteristics and demonstrate high antibacterial potential that highlights them as promising alternatives against a wide range of pathogens. The immense antibacterial potential of AgNPs is primarily attributed to the release of silver ions that lead to the
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Silver nanoparticles (AgNPs) possess distinct physicochemical characteristics and demonstrate high antibacterial potential that highlights them as promising alternatives against a wide range of pathogens. The immense antibacterial potential of AgNPs is primarily attributed to the release of silver ions that lead to the disruption of bacterial cell membrane, generation of reactive oxygen species (ROS), inhibition of protein synthesis and interference with DNA replication. Variations in AgNPs’ shape, size, and surface characteristics are also considered key factors determining their effectivity as well as specificity. AgNPs are considered potent antibacterial agents, including against antibiotic- and drug-resistant strains. However, inappropriate dosages or unoptimized application of may result in potential toxicity, consisting one of the main drawbacks of the AgNPs’ safer administration. This article reviews the recent literature on the antibacterial potential of AgNPs, focusing on their broad mechanisms of action, applicability, especially in agriculture, biomedical and environmental fields, toxicity and future perspectives.
Full article
(This article belongs to the Special Issue Innovative Nanomaterials from Functional Molecules)
Open AccessReview
Spatiotemporal Regulation and Lineage Specification in Embryonic Endochondral Ossification
by
Sixun Wu, Keita Kondo and Yuki Matsushita
Int. J. Mol. Sci. 2026, 27(2), 926; https://doi.org/10.3390/ijms27020926 (registering DOI) - 16 Jan 2026
Abstract
Long bone formation in vertebrates proceeds via endochondral ossification, a sequential process that begins with mesenchymal condensation, advances through cartilage anlage formation, and culminates in its replacement by mineralized bone. Recent advances in inducible lineage tracing and single-cell genomics have revealed that, rather
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Long bone formation in vertebrates proceeds via endochondral ossification, a sequential process that begins with mesenchymal condensation, advances through cartilage anlage formation, and culminates in its replacement by mineralized bone. Recent advances in inducible lineage tracing and single-cell genomics have revealed that, rather than being a uniform event, mesenchymal condensation rapidly segregates into progenitor pools with distinct fates. Centrally located Sox9+/Fgfr3+ chondroprogenitors expand into the growth plate and metaphyseal stroma, peripheral Hes1+ boundary cells refine condensation via asymmetric division, and outer-layer Dlx5+ perichondrial cells generate the bone collar and cortical bone. Concurrently, dorsoventral polarity established by Wnt7a–Lmx1b and En1 ensures that dorsal progenitors retain positional identity throughout development. These lineage divergences integrate with signaling networks, including the Ihh–PTHrP, FGF, BMPs, and WNT/β-catenin networks, which impose temporal control over chondrocyte proliferation, hypertrophy, and vascular invasion. Perturbations in these programs, exemplified by mutations in Fgfr3, Sox9, and Dlx5, underlie region-specific skeletal dysplasias, such as achondroplasia, campomelic dysplasia, and split-hand/foot malformation, demonstrating the lasting impacts of embryonic patterning errors. Based on these insights, regenerative strategies are increasingly drawing upon developmental principles, with organoid cultures recapitulating ossification centers, biomimetic hydrogels engineered for spatiotemporal morphogen delivery, and stem cell- or exosome-based therapies harnessing developmental microRNA networks. By bridging developmental biology with biomaterials science, these approaches provide both a roadmap to unravel skeletal disorders and a blueprint for next-generation therapies to reconstruct functional bones with the precision of the embryonic blueprint.
Full article
(This article belongs to the Collection Feature Papers in Molecular Pathology, Diagnostics, and Therapeutics)
Open AccessArticle
Ferulic Acid Attenuates Heat Stress-Induced Hepatic and Intestinal Oxidative Stress and Cholesterol Metabolism Dysregulation in Juvenile Blunt Snout Bream (Megalobrama amblycephala)
by
Yan Lin, Xiangjun Leng, Linjie Qian, Linghong Miao, Xiaoqin Li, Wenqiang Jiang, Siyue Lu and Zhengyan Gu
Int. J. Mol. Sci. 2026, 27(2), 925; https://doi.org/10.3390/ijms27020925 (registering DOI) - 16 Jan 2026
Abstract
Ferulic acid (FA) is a green feed additive. To investigate the molecular mechanisms by which FA attenuates heat stress-induced hepatic and intestinal oxidative stress, as well as cholesterol metabolism disorders in Megalobrama amblycephala (9.75 ± 0.04 g), individuals were fed diets supplemented with
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Ferulic acid (FA) is a green feed additive. To investigate the molecular mechanisms by which FA attenuates heat stress-induced hepatic and intestinal oxidative stress, as well as cholesterol metabolism disorders in Megalobrama amblycephala (9.75 ± 0.04 g), individuals were fed diets supplemented with 0, 100, or 200 mg/kg FA for eight weeks, followed by exposure to heat stress at 34 °C for 48 h. The results indicated that FA supplementation reduced malondialdehyde levels and downregulation genes involved in inflammatory responses (e.g., interleukin-6), apoptosis (e.g., caspase 8), and endoplasmic reticulum stress (e.g., immunoglobulin binding protein) (p < 0.05), which collectively alleviated heat stress-induced hepatic and intestinal oxidative stress. FA supplementation increased the expression of ATP-binding cassette transporter A1, apolipoprotein A1, and liver X receptor α (p < 0.05), and restored liver and plasma TC levels to pre-stress levels (p < 0.05). Additionally, FA ameliorated the heat stress-induced dysbiosis of the intestinal microbiota and modulated the composition and abundance of metabolites in intestinal contents and plasma, some of which are associated with cholesterol metabolism. In conclusion, dietary FA can alleviate heat stress-induced hepatic and intestinal oxidative stress, maintain the stability of the intestinal microbiota and regulate metabolic profiles, and improve the cholesterol metabolism disorders caused by heat stress.
Full article
(This article belongs to the Special Issue New Perspectives on Fish Nutrition, Physiology and Molecular Regulatory Networks)
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Open AccessArticle
Intravitreal Dexamethasone Implant in Retinal Vein Occlusion: A Pilot Study Exploring Baseline Ocular and Circulating Biomarkers
by
Carlo Gesualdo, Settimio Rossi, Fabiana Anna D’Agostino, Rosalba Casaburi, Maria Consiglia Trotta, Caterina Claudia Lepre, Marina Russo, Michele D’Amico and Francesca Simonelli
Int. J. Mol. Sci. 2026, 27(2), 924; https://doi.org/10.3390/ijms27020924 (registering DOI) - 16 Jan 2026
Abstract
This pilot study assessed the effectiveness of the intravitreal dexamethasone implant (Ozurdex) in retinal vein occlusion (RVO) patients and explored potential pre-treatment biomarkers to improve management and prognosis. Eighteen patients with branch RVO (BRVO) and twenty-four with central RVO (CRVO) receiving two intravitreal
[...] Read more.
This pilot study assessed the effectiveness of the intravitreal dexamethasone implant (Ozurdex) in retinal vein occlusion (RVO) patients and explored potential pre-treatment biomarkers to improve management and prognosis. Eighteen patients with branch RVO (BRVO) and twenty-four with central RVO (CRVO) receiving two intravitreal injections of Ozurdex (at baseline and between 4 and 6 months) were included. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were recorded at baseline and after 3, 6, and 12 months. Retinal morphology was assessed using optical coherence tomography (OCT), and serum biomarkers were analyzed by ELISAs. No significant BCVA improvement was observed in RVO patients, while CRT significantly decreased from 3 to 12 months. Patients without defects of the retinal inner layers, ellipsoid zone, and external limiting membrane showed significantly higher BCVA at 6 and 12 months. Both BRVO and CRVO groups demonstrated significant BCVA improvement and CRT reduction at 6 and 12 months, with better outcomes in BRVO patients. These patients exhibited lower baseline serum levels of xanthine oxidase (XO) and thrombospondin-1 (TSP-1), which inversely correlated with BCVA at 12 months. Ozurdex was effective in real-life RVO treatment, particularly in BRVO. Serum XO and TSP-1 may serve as prognostic biomarkers for RVO.
Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Retinal Diseases)
Open AccessArticle
Investigation of the Relationships Between IL-12B and IL-23 Receptor Polymorphisms with Behçet’s Disease in a Turkish Population
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Sanem Arıkan, Onur Öztürk, Ayfer Atalay and Erol Ömer Atalay
Int. J. Mol. Sci. 2026, 27(2), 923; https://doi.org/10.3390/ijms27020923 (registering DOI) - 16 Jan 2026
Abstract
Behçet’s disease is a chronic, multisystem inflammatory disorder characterized by recurrent mucocutaneous and ocular manifestations, in which genetic factors, particularly cytokine gene polymorphisms, are thought to contribute to disease susceptibility. This study aimed to investigate the association of Interleukin-12B and Interleukin-23R gene polymorphisms
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Behçet’s disease is a chronic, multisystem inflammatory disorder characterized by recurrent mucocutaneous and ocular manifestations, in which genetic factors, particularly cytokine gene polymorphisms, are thought to contribute to disease susceptibility. This study aimed to investigate the association of Interleukin-12B and Interleukin-23R gene polymorphisms and haplotype distributions with Behçet’s disease in Denizli, a province of Turkey. A total of 88 patients with Behçet’s disease and 133 healthy controls were genotyped for Interleukin-12B (rs3213119, rs3213120, rs3212227, rs3213113, rs2082412) and Interleukin-23R (rs1004819, rs7517847, rs7530511, rs10489629, rs10889677) polymorphisms using polymerase chain reaction–restriction fragment length polymorphism analysis. Genotype, allele, and haplotype distributions were evaluated for associations with Behçet’s disease risk and clinical manifestations. The results demonstrated that the Interleukin-12B rs2082412 G allele and rs3213119 G allele were associated with increased risk of Behçet’s disease. Additionally, the Interleukin-23R rs7530511 TT genotype and rs10489629 GG genotype and G allele were significantly associated with Behçet’s disease susceptibility. Haplotype analyses revealed AAAGG and GTCAC as the most frequent haplotypes in Interleukin-12B and Interleukin-23R loci, respectively, in both patients and controls. These findings suggest that Interleukin-12B and Interleukin-23R gene polymorphisms and haplotypes may be associated with Behçet’s disease susceptibility and clinical heterogeneity in this population.
Full article
Open AccessArticle
Circulating Naïve Regulatory T Cell Subset Displaying Increased STAT5 Phosphorylation During Controlled Ovarian Hyperstimulation Is Associated with Clinical Pregnancy and Progesterone Levels
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Ksenija Rakić, Aleš Goropevšek, Nejc Kozar, Borut Kovačič, Sara Čurič, Andreja Zakelšek, Evgenija Homšak and Milan Reljič
Int. J. Mol. Sci. 2026, 27(2), 922; https://doi.org/10.3390/ijms27020922 (registering DOI) - 16 Jan 2026
Abstract
Regulatory T cells (Tregs), particularly their phenotypically distinct subpopulations, are critical for the establishment of maternal immune tolerance during embryo implantation. Despite advances in assisted reproductive technologies, implantation failure remains a frequent and often unexplained clinical challenge. Variations in Treg frequency and phenotype
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Regulatory T cells (Tregs), particularly their phenotypically distinct subpopulations, are critical for the establishment of maternal immune tolerance during embryo implantation. Despite advances in assisted reproductive technologies, implantation failure remains a frequent and often unexplained clinical challenge. Variations in Treg frequency and phenotype have been proposed to influence implantation success, particularly under differing hormonal conditions. This study aimed to investigate peripheral blood Treg levels and their subpopulations on the day of blastocyst transfer in both stimulated in vitro fertilization (IVF/ICSI) cycles involving controlled ovarian hyperstimulation (COH) and true natural cycles with frozen embryo transfer (FET), and to examine their associations with systemic hormone levels and anti-Müllerian hormone (AMH). A prospective observational study was conducted including women undergoing IVF/ICSI with fresh embryo transfer (ET) and women undergoing natural cycle FET. Peripheral blood samples were collected on the day of ET and analyzed using 13-colour flow cytometry, enabling detailed subdivision of Tregs into multiple subpopulations based on the expression of differentiation and chemokine markers, including CXCR5. In addition, because common -chain cytokines may influence pregnancy success by modulating the balance between suppressive Treg and non-Treg subsets, intracellular STAT5 signaling was assessed using phospho-specific flow cytometry. Serum estradiol, progesterone, FSH, LH, and AMH levels were measured in parallel. Significant differences were observed in Treg subpopulation distributions between women who conceived and those who did not. Higher frequencies of naïve CXCR5− Tregs were associated with clinical pregnancy, independent of age, and correlated with serum progesterone levels. Moreover, both naïve Treg frequency and enhanced IL-7-dependent STAT5 signaling in naïve Tregs from women undergoing COH were associated with AMH levels, suggesting a link between ovarian reserve and Treg homeostasis mediated by signal transducer and activator of transcription 5 (STAT5) signaling. In conclusion, Treg subpopulations, particularly CXCR5− naïve Tregs, appear to play a central role in implantation success following ET. Their distribution differs between stimulated and natural cycles and is influenced by systemic progesterone levels and STAT5 signaling. These findings suggest that peripheral Treg profiling may represent a potential biomarker of implantation competence and could inform personalized approaches in assisted reproduction.
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(This article belongs to the Section Molecular Biology)
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Open AccessReview
Angiopoietin-like Protein 3 (ANGPTL3) Targeting in the Management of Dyslipidemias
by
Constantine E. Kosmas, Loukianos S. Rallidis, Ioannis Hoursalas, Evangelia J. Papakonstantinou and Christina E. Kostara
Int. J. Mol. Sci. 2026, 27(2), 921; https://doi.org/10.3390/ijms27020921 - 16 Jan 2026
Abstract
Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality, despite advances in pharmacological prevention and treatment. The burden of CVD necessitates implementing the treatment of risk factors including dyslipidemia. Pharmaceutical advancements and in depth understanding of pathophysiology have enabled innovative therapies
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Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality, despite advances in pharmacological prevention and treatment. The burden of CVD necessitates implementing the treatment of risk factors including dyslipidemia. Pharmaceutical advancements and in depth understanding of pathophysiology have enabled innovative therapies targeting pathways underlying lipoprotein metabolism disorders. Angiopoietin protein-like 3 (ANGPTL3) plays a crucial role in the regulation of lipoprotein metabolism, therefore being a potential therapeutic target. Inhibition of ANGPTL3 has emerged as a new therapeutic strategy to reduce LDL-cholesterol levels independent of the LDL receptor function. Therapeutic approaches for ANGPTL3 inhibition range from monoclonal antibodies to nucleic acid therapeutics including antisense oligonucleotides and small interfering RNAs. In this review, we briefly explain the structure and mechanism of action of ANGPTL3 and discuss the therapeutic approaches for targeting ANGPTL3 in the clinical setting. We also discuss Evinacumab, a monoclonal antibody, its structure, mechanism of action, safety, tolerability, pharmacokinetics, and pharmacodynamics, as well as its clinical trial-derived results. The antisense oligonucleotides modify ANGPTL3 mRNA to inhibit protein production, and small interfering RNAs induce mRNA degradation; results from clinical trials were reviewed in detail. Finally, we discuss promising gene editing approaches including clustered regularly interspaced short palindromic repeats (CRISPR)/Cas systems.
Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Open AccessArticle
Identification of SNPs in the NKA Gene of Scylla paramamosain and the Association Analysis with Low-Salinity Tolerance
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Chunyan Yin, Zhiqiang Liu, Keyi Ma, Wei Wang, Lingxiao Wang, Lingbo Ma, Chunyan Ma and Fengying Zhang
Int. J. Mol. Sci. 2026, 27(2), 920; https://doi.org/10.3390/ijms27020920 - 16 Jan 2026
Abstract
The Na+/K+-ATPase (NKA) gene encodes a critical membrane transporter that maintains cellular ion homeostasis and plays a pivotal role in osmoregulation and salinity adaptation of aquatic organisms. In this study, we identified and validated SNP markers in the NKA
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The Na+/K+-ATPase (NKA) gene encodes a critical membrane transporter that maintains cellular ion homeostasis and plays a pivotal role in osmoregulation and salinity adaptation of aquatic organisms. In this study, we identified and validated SNP markers in the NKA gene associated with low-salinity tolerance in Scylla paramamosain. Four candidate SNPs (g.72037G>T, g.72122G>C, g.74293G>T, and g.74433G>T) were screened and genotyped in low-salinity tolerant and intolerant groups. Association analysis revealed that mutant genotypes at all four loci were significantly enriched in the tolerant group (p < 0.05), with odds ratios (OR) > 1. The tolerant group exhibited higher genetic diversity parameters than the intolerant group. Haplotype analysis showed the GGGG haplotype was dominant in the intolerant group, whereas the other haplotypes were mainly enriched in the tolerant group. The NKA expression in the mutant genotypes was significantly higher than that in the wild genotypes by qRT-PCR. For tolerant individuals, the fast-growing group exhibited higher mutation frequencies than the slow-growing group. Multi-locus analysis achieved substantially more discrimination accuracy than single-locus analysis. These findings demonstrated that these SNPs could be candidate molecular markers for breeding programs in S. paramamosain in low-salinity environments, helping to identify individuals with enhanced salinity tolerance and supporting sustainable aquaculture practices.
Full article
(This article belongs to the Section Molecular Biology)
Open AccessReview
The Placenta in Gestational Diabetes: An Integrated Review on Metabolic Pathways, Genetic, Epigenetic and Ultrasound Biomarkers for Clinical Perspectives
by
Giovanni Tossetta, Roberto Campagna, Arianna Vignini, Giuseppe Maria Maruotti, Mariarosaria Motta, Chiara Murolo, Laura Sarno, Camilla Grelloni, Monia Cecati, Stefano Raffaele Giannubilo and Andrea Ciavattini
Int. J. Mol. Sci. 2026, 27(2), 919; https://doi.org/10.3390/ijms27020919 - 16 Jan 2026
Abstract
Pregnancies complicated by diabetes, including pregestational and gestational diabetes mellitus, are associated with increased maternal and fetal morbidity. Early identification of at-risk pregnancies is crucial for timely intervention and improved outcomes. Emerging evidence highlights the interplay of genetic predisposition, epigenetic modifications, and non-invasive
[...] Read more.
Pregnancies complicated by diabetes, including pregestational and gestational diabetes mellitus, are associated with increased maternal and fetal morbidity. Early identification of at-risk pregnancies is crucial for timely intervention and improved outcomes. Emerging evidence highlights the interplay of genetic predisposition, epigenetic modifications, and non-invasive biomarkers in the early detection of diabetic pregnancies. Genetic factors influencing insulin signaling, glucose metabolism, and pancreatic β-cell function may contribute to susceptibility to gestational hyperglycemia. Concurrently, epigenetic alterations, such as DNA methylation and histone modifications in maternal and placental tissues, have been linked to dysregulated metabolic pathways and adverse pregnancy outcomes. Non-invasive biomarkers, including circulating cell-free DNA and microRNAs in maternal blood, show promise for early diagnosis by offering a safer and more practical alternative to invasive testing. Integrating genetic, epigenetic, and molecular marker data could enhance risk stratification and enable personalized monitoring and management strategies. This review synthesizes current knowledge on the molecular underpinnings of diabetic pregnancies, evaluates the potential of emerging biomarkers for early diagnosis, and discusses the challenges and future perspectives for translating these findings into clinical practice. Understanding these mechanisms may pave the way for precision medicine approaches, ultimately improving maternal and neonatal outcomes in pregnancies affected by diabetes.
Full article
(This article belongs to the Collection Latest Review Papers in Molecular Pathology, Diagnostics, and Therapeutics)
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Lipid Droplets in Cancer: New Insights and Therapeutic Potential
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Shriya Joshi, Chakravarthy Garlapati, Amartya Pradhan, Komal Gandhi, Adepeju Balogun and Ritu Aneja
Int. J. Mol. Sci. 2026, 27(2), 918; https://doi.org/10.3390/ijms27020918 - 16 Jan 2026
Abstract
The progression of neoplastic diseases is driven by a complex interplay of biological processes, including uncontrolled proliferation, enhanced invasion, metastasis, and profound metabolic reprogramming. Among the hallmarks of cancer, as revised by Hanahan and Weinberg, the reprogramming of energy metabolism has emerged as
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The progression of neoplastic diseases is driven by a complex interplay of biological processes, including uncontrolled proliferation, enhanced invasion, metastasis, and profound metabolic reprogramming. Among the hallmarks of cancer, as revised by Hanahan and Weinberg, the reprogramming of energy metabolism has emerged as a critical feature that enables cancer cells to meet their heightened bioenergetic and biosynthetic demands. One significant aspect of this metabolic adaptation is the accumulation of lipid droplets (LDs) dynamic, cytoplasmic organelles primarily involved in lipid storage and metabolic regulation. LDs serve as reservoirs of neutral lipids and play a multifaceted role in cancer cell physiology. Their accumulation is increasingly recognized as a marker of tumor aggressiveness and poor prognosis. By storing lipids, LDs provide a readily accessible source of energy and essential building blocks for membrane synthesis, supporting rapid cell division and growth. Moreover, LDs contribute to cellular homeostasis by modulating oxidative stress, maintaining redox balance, and regulating autophagy, particularly under nutrient-deprived or hypoxic conditions commonly found in the tumor microenvironment. Importantly, LDs have been implicated in the development of resistance to cancer therapies. They protect cancer cells from the cytotoxic effects of chemotherapeutic agents by buffering endoplasmic reticulum (ER) stress, inhibiting apoptosis, and facilitating survival pathways. The presence of LDs has been shown to correlate with increased resistance to a variety of chemotherapeutic drugs, although the precise molecular mechanisms underlying this phenomenon remain incompletely understood. Emerging evidence suggests that chemotherapy itself can induce changes in LD accumulation, further complicating treatment outcomes. Given their central role in cancer metabolism and therapy resistance, LDs represent a promising target for therapeutic intervention. Strategies aimed at disrupting lipid metabolism or inhibiting LD biogenesis have shown potential in sensitizing cancer cells to chemotherapy and overcoming drug resistance. In this review, we comprehensively examine the current understanding of LD biology in cancer, highlight studies that elucidate the link between LDs and drug resistance, and discuss emerging approaches to target lipid metabolic pathways to enhance therapeutic efficacy across diverse cancer types.
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(This article belongs to the Special Issue Cancer Biomarkers and Metabolic Vulnerabilities)
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Antibiotic-Mediated Modulation of the Gut Microbiome Identifies Taurine as a Modulator of Adipocyte Function Through TGR5 Signaling
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Elisabeth Jäger, Viktoriya Peeva, Thorsten Gnad, Sven-Bastiaan Haange, Ulrike Rolle-Kampczyk, Claudia Stäubert, Petra Krumbholz, John T. Heiker, Claudia Gebhardt, Ute Krügel, Paromita Sen, Monika Harazin, Viktoria Stab, Julia Münzker, Nazha Hamdani, Alexander Pfeifer, Martin von Bergen, Andreas Till and Wiebke K. Fenske
Int. J. Mol. Sci. 2026, 27(2), 917; https://doi.org/10.3390/ijms27020917 - 16 Jan 2026
Abstract
Gut microbiota has emerged as a modulator of host metabolism and energy balance. However, the precise microbial metabolites mediating thermogenic activation in obesity remain largely undefined. We investigated the effect of antibiotic treatment under a high-fat diet on metabolites and its contribution to
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Gut microbiota has emerged as a modulator of host metabolism and energy balance. However, the precise microbial metabolites mediating thermogenic activation in obesity remain largely undefined. We investigated the effect of antibiotic treatment under a high-fat diet on metabolites and its contribution to lipolysis and thermogenesis. Antibiotic treatment in high-fat diet-fed rats reduced adiposity and enhanced adaptive thermogenesis. Metabolomics revealed elevated taurine levels in the cecum content and plasma of antibiotic-treated animals, correlating with increased expressions of UCP1 and TGR5 in brown adipose tissue. Taurine enhanced lipolysis and oxygen consumption in mouse adipose tissue and human adipocytes. Thereby, taurine modulated lipolysis dependent on TGR5 signaling in adipose tissue. Human data confirmed that taurine promotes browning of white adipocytes and that acute cold exposure leads to a marked drop in circulating taurine, suggesting its rapid recruitment into thermogenic tissues. Besides its synthesis in the liver and dietary uptake, taurine can be a microbiota-derived metabolite that activates adipose thermogenesis and lipolysis through TGR5 and possibly taurine transporter-dependent mechanisms. These findings uncover a gut–adipose axis with therapeutic potential for metabolic disease.
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(This article belongs to the Section Molecular Endocrinology and Metabolism)
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Pharmacologic Modulation of the PAR-2–ERK Axis by Statins Converts Inflammatory Survival Signalling into Apoptosis in Colorectal Cancer Cells
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Layla Amiri, Rajashree Patnaik, Riah Lee Varghese, Bintul Huda and Yajnavalka Banerjee
Int. J. Mol. Sci. 2026, 27(2), 916; https://doi.org/10.3390/ijms27020916 - 16 Jan 2026
Abstract
Chronic inflammation constitutes a well-established driver of colorectal carcinogenesis, yet the molecular circuitry linking inflammatory receptor signalling to tumour cell survival remains incompletely delineated. Here we demonstrate that the HMG-CoA reductase inhibitors atorvastatin and rosuvastatin modulate inflammatory survival pathways in colorectal cancer cells
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Chronic inflammation constitutes a well-established driver of colorectal carcinogenesis, yet the molecular circuitry linking inflammatory receptor signalling to tumour cell survival remains incompletely delineated. Here we demonstrate that the HMG-CoA reductase inhibitors atorvastatin and rosuvastatin modulate inflammatory survival pathways in colorectal cancer cells in a manner consistent with targeted interference with the protease-activated receptor 2 (PAR-2)–extracellular signal-regulated kinase (ERK)–tumour necrosis factor-α (TNF-α) signalling axis. Using lipopolysaccharide-stimulated HT-29 and Caco-2 cells as complementary models of inflammatory colorectal malignancy, we show that both statins selectively attenuate PAR-2 expression at the protein and transcript levels while leaving structurally related PAR-1 unaffected. This pattern of receptor modulation is accompanied by suppression of total ERK1/2 expression, ERK1/2 phosphorylation, and the transcriptional target DUSP6, together with attenuation of TNF-α secretion. Importantly, these signaling shifts are associated with dual apoptotic programs; the extrinsic pathway, reflected by transcriptional upregulation and proteolytic activation of caspase-8; and the intrinsic mitochondrial pathway, evidenced by reciprocal modulation of Bcl-2 family proteins favoring Bax over Bcl-2. Both pathways converge upon activation of executioner caspase-3 and an increase in Annexin V-defined apoptotic fractions, indicating re-engagement of programmed cell death under inflammatory stress. Notably, rosuvastatin consistently demonstrates superior potency across signaling endpoints, achieving comparable biological effects at lower concentrations than atorvastatin. Collectively, these data indicate that clinically deployed statins target the PAR-2–ERK axis and are associated with re-activation of apoptotic pathways in inflammatory colorectal cancer models, while leaving open the possibility that additional statin-responsive networks contribute to their pro-apoptotic effects. This mechanistic framework provides biological plausibility for epidemiologic observations linking statin use with reduced colorectal cancer risk and improved outcomes, and supports further translational evaluation of PAR-2-directed statin strategies in colorectal malignancy.
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(This article belongs to the Special Issue Colorectal Cancer—Emerging Trends and Treatment Strategies)
Open AccessReview
Enhancing the Water Solubility and Efficacy of Anticancer Drugs Using Hydroxypropyl-β-Cyclodextrin
by
Yasushi Kubota and Shinya Kimura
Int. J. Mol. Sci. 2026, 27(2), 915; https://doi.org/10.3390/ijms27020915 - 16 Jan 2026
Abstract
Cyclodextrins (CyDs) are cyclic oligosaccharides that form inclusion complexes that allow organic compounds and other substances to be incorporated into their cavities. Hydroxypropyl-β-cyclodextrin (HP-β-CyD) is frequently used to improve the formulation properties of poorly water-soluble drugs because of its aqueous solubility and biocompatibility.
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Cyclodextrins (CyDs) are cyclic oligosaccharides that form inclusion complexes that allow organic compounds and other substances to be incorporated into their cavities. Hydroxypropyl-β-cyclodextrin (HP-β-CyD) is frequently used to improve the formulation properties of poorly water-soluble drugs because of its aqueous solubility and biocompatibility. Previous studies have demonstrated that the solubility and biocompatibility of poorly water-soluble anti-cancer agents can be improved by complexation with HP-β-CyD, which in some cases enhances their anticancer activity relative to the unmodified drugs. Advances in formulation strategies have enabled more efficient intracellular delivery, improved tissue and cell selectivity, and controlled release. HP-β-CyD has also been investigated as an active pharmaceutical ingredient, with demonstrated efficiency in treating leukemia and breast cancer. For example, folate-conjugated HP-β-CyD exhibits high selectivity for folate receptor-expressing cells and more potent anti-cancer activity than unmodified HP-β-CyD. Autophagy has been suggested to be involved in this mechanism. The continued development of drug-delivery systems that integrate advanced technologies and materials based on HP-β-CyD holds promise for further advances in cancer therapy. These findings indicate a paradigm shift in the role of HP-β-CyD from a formulation additive to an active pharmaceutical ingredient, suggesting broader applications for HP-β-CyD in anticancer treatments.
Full article
(This article belongs to the Special Issue Cyclodextrins: Properties and Applications, 3rd Edition)
Open AccessReview
Different Approaches to Oral Lichen Planus Treatment: A Narrative Review
by
Irena Duś-Ilnicka, Andrzej Małysa, Marta Mazur and Anna Paradowska-Stolarz
Int. J. Mol. Sci. 2026, 27(2), 914; https://doi.org/10.3390/ijms27020914 - 16 Jan 2026
Abstract
Oral lichen planus (OLP) is a chronic immune-mediated disorder affecting the mucous membranes of the oral cavity, characterized by inflammation caused by T-cell-mediated destruction of basal keratinocytes with the potential for malignant transformation. The exact etiology of the disease remains unclear, but as
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Oral lichen planus (OLP) is a chronic immune-mediated disorder affecting the mucous membranes of the oral cavity, characterized by inflammation caused by T-cell-mediated destruction of basal keratinocytes with the potential for malignant transformation. The exact etiology of the disease remains unclear, but as its symptoms may reduce patient quality of life, various treatment modalities have been proposed, generally based on managing symptoms and controlling disease progression. In this narrative review, we examine both conventional therapies (corticosteroids, immunosuppressants, retinoids) and emerging treatment options (photodynamic therapy, low-level laser therapy, and biologics) in terms of their efficacy and limitations. Although corticosteroid therapy remains a cornerstone of treatment, it is not effective in all cases, demonstrating the need to investigate alternative methods; hence, we also present possible future directions for OLP treatment in this study.
Full article
(This article belongs to the Special Issue Oral Soft Tissue Repair and Oral Diseases: 2nd Edition)
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Open AccessArticle
Heritability and Transcriptional Impact of JAK3, STAT5A and STAT6 Variants in a Tyrolean Family
by
Hye Kyung Lee, Teemu Haikarainen, Yasemin Caf, Priscilla A. Furth, Ludwig Knabl, Olli Silvennoinen and Lothar Hennighausen
Int. J. Mol. Sci. 2026, 27(2), 913; https://doi.org/10.3390/ijms27020913 (registering DOI) - 16 Jan 2026
Abstract
The Janus Kinase (JAK) and Signal Transducers and Activators of Transcription (STAT) pathways regulate a range of biological processes, including immune response and hematopoiesis. While a major research focus has been on somatic human mutations in disease, less is known about the heritability
[...] Read more.
The Janus Kinase (JAK) and Signal Transducers and Activators of Transcription (STAT) pathways regulate a range of biological processes, including immune response and hematopoiesis. While a major research focus has been on somatic human mutations in disease, less is known about the heritability of germline variants and their physiological impact. This study addresses an important issue in population genetics: the context-dependent effects and incomplete penetrance of rare genetic variants in immune pathways. Here we identify the rare JAK3P151R, JAK3R925S, STAT5AV494L, and STAT6Q633H variants in an extended family spanning three generations, integrate in silico analyses and AlphaFold 3 structural predictions, and investigate the immune transcriptomes in probands carrying one or more variants. All four variants are inherited through the germline without any evident clinical or physiological manifestations in the carriers. As individual variants, not all persons carrying a specific variant showed the same immune transcriptome. The presence of activated basal transcriptomes was limited to some, but not all, individuals carrying the above variants. A next step in understanding the role of germline variants will be to understand how and why other factors, including both other germline variants and environmental and developmental factors, influence the likelihood of expression of an activated basal transcriptome.
Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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Open AccessArticle
Genome-Wide Identification and Evolutionary Analysis of the bHLH Transcription Factor Family in Rosa roxburghii
by
Yuan-Yuan Li, Li-Zhen Ling and Shu-Dong Zhang
Int. J. Mol. Sci. 2026, 27(2), 912; https://doi.org/10.3390/ijms27020912 - 16 Jan 2026
Abstract
The basic/helix-loop-helix (bHLH) transcription factors are crucial regulators of plant development and stress responses. In this study, we conducted a genome-wide analysis of the bHLH family in Rosa roxburghii, an economically important fruit crop. A total of 89 non-redundant RrbHLHs were identified
[...] Read more.
The basic/helix-loop-helix (bHLH) transcription factors are crucial regulators of plant development and stress responses. In this study, we conducted a genome-wide analysis of the bHLH family in Rosa roxburghii, an economically important fruit crop. A total of 89 non-redundant RrbHLHs were identified and unevenly distributed across the seven chromosomes. Phylogenetic analysis classified them into 23 subfamilies and 7 Arabidopsis subfamilies were absent, indicating lineage-specific evolutionary trajectories. Conserved motif and gene structure analyses showed that members within the same subfamily generally shared similar architectures, yet subfamily-specific variations were evident, suggesting potential functional diversification. Notably, key residues involved in DNA-binding and dimerization were highly conserved within the bHLH domain. Promoter analysis identified multiple cis-acting elements related to hormone response, stress adaptation, and tissue-specific regulation, hinting at broad regulatory roles. Expression profiling across fruit developmental stages and in response to GA3 treatment revealed dynamic expression patterns. Furthermore, 21 duplicated gene pairs (17 segmental and 4 tandem duplicated pairs) were identified, with most evolving under purifying selection. Detailed analysis of these pairs revealed that segmental duplication, coupled with structural variations such as exon indels, dissolution/joining, and exonization/pseudoexonization, substantially contributed to their functional divergence during evolution. Our results provide a basis for understanding the evolution and potential functions of the RrbHLHs.
Full article
(This article belongs to the Special Issue Transcription Factors in Plant Gene Expression Regulation, 2nd Edition)
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Open AccessArticle
Crocins Ameliorate Experimental Immune Checkpoint Inhibitor-Related Myocarditis by Targeting the Hpx/Nrf2/HO-1 Pathway
by
Jing Yan, Qingqing Cai, Yu Li, Yi Zhang, Ye Zhao, Fangbo Zhang and Huamin Zhang
Int. J. Mol. Sci. 2026, 27(2), 911; https://doi.org/10.3390/ijms27020911 - 16 Jan 2026
Abstract
Immune checkpoint inhibitors (ICIs) for cancer therapy may induce immune-related adverse events including myocarditis, which occurs infrequently but carries a high mortality rate. Crocins are the active constituents derived from Crocus sativus L. (saffron), and have demonstrated various bioactivities including anti-tumor, anti-inflammation, antioxidation,
[...] Read more.
Immune checkpoint inhibitors (ICIs) for cancer therapy may induce immune-related adverse events including myocarditis, which occurs infrequently but carries a high mortality rate. Crocins are the active constituents derived from Crocus sativus L. (saffron), and have demonstrated various bioactivities including anti-tumor, anti-inflammation, antioxidation, anti-ischemia, anti-aging, and neuroprotective effects. This study established a subcutaneous xenotransplanted tumor model of human liver cancer in nude mice to better mimic ICI-related myocarditis. Animal experimental results revealed that crocins improved cardiac function, relieved myocardial damage and autoimmune response, and suppressed oxidative stress and inflammatory reaction. Quantitative proteomics and Western blotting verification confirmed that crocins ameliorated experimental ICI-related myocarditis by targeting the Hpx/Nrf2/HO-1 pathway. Molecular docking revealed that the best docking activities were demonstrated by crocin I–HO-1, crocin II–Hpx, and crocin III–Nrf2. These findings shed new light on the development of therapeutic strategies for treating ICI-related myocarditis and provided the fundamental basis for expanding the clinical application of crocins.
Full article
(This article belongs to the Section Molecular Pharmacology)
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Open AccessArticle
Hybrid Fe3O4-Gd2O3 Nanoparticles Prepared by High-Energy Ball Milling for Dual-Contrast Agent Applications
by
Vladislav A. Mikheev, Timur R. Nizamov, Alexander I. Novikov, Maxim A. Abakumov, Alexey S. Lileev and Igor V. Shchetinin
Int. J. Mol. Sci. 2026, 27(2), 910; https://doi.org/10.3390/ijms27020910 - 16 Jan 2026
Abstract
This work investigates the feasibility of synthesis hybrid x Gd2O3 + (100 − x) Fe3O4 nanoparticles using the scalable method of high-energy ball milling for dual-contrast magnetic resonance imaging applications. Comprehensive studies of the structure, magnetic and
[...] Read more.
This work investigates the feasibility of synthesis hybrid x Gd2O3 + (100 − x) Fe3O4 nanoparticles using the scalable method of high-energy ball milling for dual-contrast magnetic resonance imaging applications. Comprehensive studies of the structure, magnetic and functional properties of the hybrid nanoparticles were conducted. It was found that the milling process initiates the transformation of the cubic phase c-Gd2O3 ( ) into the monoclinic m-Gd2O3 (C2/m). Measurements of the magnetic properties showed that the specific saturation magnetization of the Fe3O4 phase is substantially reduced, which is a characteristic feature of nanoparticles due to phenomena such as surface spin disorder and spin-canting effects. The transmission electron microscopy results confirm the formation of hybrid Fe3O4-Gd2O3 nanostructures and the measured particle sizes show good correlation with the X-ray diffraction results. A comprehensive structure–property relationship study revealed that the obtained hybrid nanoparticles exhibit high r2 values, reaching 160 mM−1s−1 and low r1 values, a characteristic that is determined primarily by the presence of a large fraction of Gd2O3 particles with sizes of ≈30 nm and Fe3O4 crystallites of ≈10 nm.
Full article
(This article belongs to the Special Issue Properties and Applications of Nanoparticles and Nanomaterials: 3rd Edition)
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