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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
From Multidimensional Management to Mechanistic Insight: A Review of Interventions for Hyperuricemia
Int. J. Mol. Sci. 2026, 27(3), 1426; https://doi.org/10.3390/ijms27031426 (registering DOI) - 30 Jan 2026
Abstract
As a major metabolic abnormality following hyperglycemia, hypertension, and hyperlipidemia, hyperuricemia has emerged as a significant global public health issue. The pathological mechanisms of hyperuricemia are complex; it not only directly triggers gout but is also closely associated with various chronic diseases, such
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As a major metabolic abnormality following hyperglycemia, hypertension, and hyperlipidemia, hyperuricemia has emerged as a significant global public health issue. The pathological mechanisms of hyperuricemia are complex; it not only directly triggers gout but is also closely associated with various chronic diseases, such as cardiovascular disease, diabetes, and chronic kidney disease, posing a systemic threat to individual health. This article systematically reviews the epidemiological characteristics, pathophysiological mechanisms, clinical consequences, and related risk factors of hyperuricemia, and especially focuses on the research advances and mechanisms of comprehensive intervention strategies, including diet, exercise, pharmacotherapy, and lifestyle modifications. Dietary interventions primarily function by regulating the activity of enzymes and transporters related to uric acid metabolism, ameliorating gut microbiota dysbiosis, and alleviating inflammatory responses. Exercise interventions synergistically improve uric acid homeostasis through multiple mechanisms, including the regulation of purine metabolic enzyme activity and the improvements of body composition, insulin resistance, and oxidative stress. Pharmacotherapy, serving as a core measure for patients with moderate-to-severe conditions, directly lowers serum uric acid levels by inhibiting uric acid production or promoting excretion. Although various intervention modalities exhibit distinct effects in regulating uric acid production, promoting excretion, and improving the metabolic-inflammatory environment, challenges such as significant heterogeneity in individual response and uncertainty regarding long-term efficacy remain prevalent. Furthermore, given the increasing trend toward a younger onset of hyperuricemia, prevention and control strategies targeting children and adolescents require urgent reinforcement. Future efforts should focus on conducting multi-center, large-sample clinical studies with clear mechanisms and establishing individualized health management plans based on population characteristics, thereby promoting the precise prevention and treatment of hyperuricemia.
Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
Open AccessArticle
PIEZO1 Mediates Apoptosis of Endothelial Cells via Enhancing HMGA2 Expression Under Simulated Microgravity
by
Yuan Wang, Ruonan Wang, Xiaodong Qin, Yikai Pan, Chengfei Li and Xiqing Sun
Int. J. Mol. Sci. 2026, 27(3), 1425; https://doi.org/10.3390/ijms27031425 - 30 Jan 2026
Abstract
Exposure to microgravity results in cardiovascular deconditioning, with endothelial cell apoptosis recognized as a pivotal initiating event. However, the mechanosensitive mechanisms underlying this process remain poorly understood. Here, we demonstrate that the expression of mechanosensitive ion channel protein PIEZO1 is upregulated in human
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Exposure to microgravity results in cardiovascular deconditioning, with endothelial cell apoptosis recognized as a pivotal initiating event. However, the mechanosensitive mechanisms underlying this process remain poorly understood. Here, we demonstrate that the expression of mechanosensitive ion channel protein PIEZO1 is upregulated in human umbilical vein endothelial cells (HUVECs) under simulated microgravity. Functional studies revealed that PIEZO1 activation promotes endothelial apoptosis under simulated microgravity conditions. Proteomic analysis following PIEZO1 knockdown revealed extensive alterations in biological processes associated with apoptosis. Furthermore, we found that PIEZO1 activation triggers calcium influx, leading to elevated expression of the HMGA2. Moreover, we identify that PIEZO1 activation induces calcium influx, which subsequently elevates the expression of HMGA2. The knockdown of HMGA2 significantly mitigated microgravity-induced endothelial apoptosis, indicating its role in PIEZO1-mediated apoptosis. These findings reveal a novel PIEZO1–Ca2+–HMGA2 axis critical for microgravity-induced endothelial apoptosis, providing mechanistic insight into cardiovascular adaptation to spaceflight and potential therapeutic targets for countermeasure development.
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(This article belongs to the Section Physical Chemistry and Chemical Physics)
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Open AccessReview
The Role of TNF-α in Ischemic Stroke
by
Renata Kołodziejska, Hanna Pawluk, Agnieszka Tafelska-Kaczmarek, Mateusz Pawluk, Krzysztof Koper, Antoni Godlewski, Julia Kuk, Krzysztof Sergot, Natalia Kurhaluk and Alina Woźniak
Int. J. Mol. Sci. 2026, 27(3), 1424; https://doi.org/10.3390/ijms27031424 - 30 Jan 2026
Abstract
Ischemic stroke accounts for approximately 80–85% of all stroke cases and triggers a complex cascade of metabolic, immunological, and neurodegenerative processes. Among the key mediators involved, TNF-α occupies a central position due to its distinctly dual and phase-dependent actions. Importantly, the biological effects
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Ischemic stroke accounts for approximately 80–85% of all stroke cases and triggers a complex cascade of metabolic, immunological, and neurodegenerative processes. Among the key mediators involved, TNF-α occupies a central position due to its distinctly dual and phase-dependent actions. Importantly, the biological effects of TNF-α are not static but evolve dynamically over time following ischemic insult. During the acute phase of ischemia, a rapid increase in TNF-α levels, primarily originating from activated microglia, leads to the predominant activation of the TNFR1 receptor. This results in enhanced apoptosis and necroptosis, disruption of the blood–brain barrier, increased leukocyte recruitment, and the progression of secondary neuronal injury. In later phases, the role of TNF-α shifts, with signaling through TNFR2 becoming more prominent, thereby supporting reparative mechanisms, including neurogenesis, angiogenesis, and synaptic remodeling. The dual nature of TNF-α means that both its excessive activation and complete inhibition may produce detrimental effects. Notably, the therapeutic relevance of TNF-α critically depends on the timing of intervention relative to stroke onset. A comprehensive analysis of current evidence underscores the central, temporally and contextually dependent role of TNF-α in the pathophysiology of ischemic stroke. It also indicates that future therapeutic strategies should aim to selectively suppress the harmful TNFR1-mediated signaling while preserving or enhancing TNFR2-dependent neuroprotective pathways. Such time-sensitive and receptor-selective modulation holds promise for limiting acute ischemic injury and promoting endogenous repair processes, representing a compelling direction for the development of next-generation neuroprotective therapies.
Full article
(This article belongs to the Special Issue Inflammatory Biomarkers in Ischemic Stroke)
Open AccessArticle
Clinical Characteristics and Molecular Profiling of SF3B1-Mutated Myelodysplastic Syndrome (MDS) in a Real-World Practice
by
Ruonan Roni Wang, Hein Than, Christopher Tham, Gee Fung How, Si Jie Khoo and Tertius T. Tuy
Int. J. Mol. Sci. 2026, 27(3), 1423; https://doi.org/10.3390/ijms27031423 - 30 Jan 2026
Abstract
SF3B1-mutated myelodysplastic syndrome (MDS) is a distinct entity associated with a favorable prognosis. Recent data suggest that certain SF3B1 variants portend a worse prognosis. Our study aims to (1) describe SF3B1-MDS patients from a single tertiary center in Singapore and (2)
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SF3B1-mutated myelodysplastic syndrome (MDS) is a distinct entity associated with a favorable prognosis. Recent data suggest that certain SF3B1 variants portend a worse prognosis. Our study aims to (1) describe SF3B1-MDS patients from a single tertiary center in Singapore and (2) determine if variant type holds prognostic value. We identified MDS patients with SF3B1 variants via next-generation sequencing (NGS) performed from 1 November 2021 to 31 October 2025 at Singapore General Hospital. Extracted genomic material from marrow or blood samples was amplified. Libraries were prepared, sequenced, and analyzed, and the hematological parameters, mutation profiles, and outcomes were evaluated. Twenty-five patients had SF3B1-MDS. Ten SF3B1 variants were found, and the three most prevalent were K700E (42%), K666N (19%), and R625C (7.7%). The median variant allele frequency (VAF) was 30% (IQR: 11–36%). Twelve patients (48%) had ≥1 co-mutations. Variant type and VAF had no impact on disease progression; only the presence of ≥1 co-mutations increased the progression chances. In our study, the analysis of SF3B1 variant type was inconclusive and showed no demonstrable statistical association with disease progression. However, the number of co-mutations affected the prognosis of patients. As SF3B1-MDS is heterogenous, further studies are needed to capture its diversity and identify features required to improve risk stratification and personalized treatment.
Full article
(This article belongs to the Special Issue New Advances in Molecular Research in Leukemia)
Open AccessReview
Common Biomarkers in Chronic Obstructive Pulmonary Disease and Bronchopulmonary Dysplasia: A Narrative Review of an Intriguing Interplay
by
Antonella Gambadauro, Federica Xerra, Valeria Chirico, Immacolata Rulli, Annalisa Cacciola, Raffaella Mallamace, Eloisa Gitto and Lucia Marina Marseglia
Int. J. Mol. Sci. 2026, 27(3), 1422; https://doi.org/10.3390/ijms27031422 - 30 Jan 2026
Abstract
Bronchopulmonary dysplasia (BPD) is a chronic lung condition in preterm infants characterized by impaired alveolar development, disrupted vascular growth, and persistent inflammation. These alterations, which often arise from early exposure to mechanical ventilation, oxygen toxicity, and infection, can lead to long-term structural and
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Bronchopulmonary dysplasia (BPD) is a chronic lung condition in preterm infants characterized by impaired alveolar development, disrupted vascular growth, and persistent inflammation. These alterations, which often arise from early exposure to mechanical ventilation, oxygen toxicity, and infection, can lead to long-term structural and functional deficits in the developing lung. In adulthood, chronic obstructive pulmonary disease (COPD) represents a major cause of morbidity and mortality and is defined by progressive airflow obstruction, reduced respiratory capacity, and chronic inflammatory responses. Although traditionally considered a disease of adult smokers, growing evidence suggests that early-life respiratory insults play a key role in shaping long-term lung health. Recent studies reveal a biologically plausible link between BPD and later COPD, indicating that premature birth, impaired lung growth, and early inflammatory injury may predispose individuals to earlier or more severe COPD development. This review explores the shared molecular pathways connecting these conditions, focusing on overlapping inflammatory biomarkers such as IL1B, IL6, IL8, TNF, TGFB, and VEGF, which collectively reflect persistent dysregulation of immune and repair mechanisms. Additionally, common genetic variants, including SERPINA1 and HHIP, may contribute to susceptibility across the lifespan. Emerging biomarkers—such as PRMT7, cathelicidin/LL-37, CRISPLD2, and GDF15—offer further insight into disease progression. Identifying these shared markers may ultimately improve early detection and help clinicians pinpoint infants with BPD who face an elevated risk of developing COPD later in life.
Full article
(This article belongs to the Special Issue Advances in Lung Research: From Mechanisms to Therapeutic Innovation)
Open AccessReview
The Emerging Role of Endothelial Ion Channels in the Control of Human Microcirculation
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Francesco Moccia, Valentina Brunetti, Roberto Berra-Romani, Giovanni Villone, Gennaro Raimo, Teresa Soda, Giorgia Scarpellino and Germano Guerra
Int. J. Mol. Sci. 2026, 27(3), 1421; https://doi.org/10.3390/ijms27031421 - 30 Jan 2026
Abstract
Endothelial ion signaling is crucial for the proper function of the arterial microcirculation, regulating local blood flow to meet metabolic demands and contributing to the regulation of systemic arterial pressure. The role of endothelial ion channels in the precise control of vascular resistance
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Endothelial ion signaling is crucial for the proper function of the arterial microcirculation, regulating local blood flow to meet metabolic demands and contributing to the regulation of systemic arterial pressure. The role of endothelial ion channels in the precise control of vascular resistance has been primarily investigated in animal models, where the microvasculature is more readily accessible. This review aims to discuss current knowledge on the role of endothelial ion signaling in vasomotor regulation in the human microcirculation, focusing on potassium (K+) channels (KIR2.1, KATP, SKCa/IKCa), Transient Receptor Potential (TRP) channels, particularly TRP Vanilloid 1 (TRPV1) and TRPV4, and Piezo1 channels. The analysis examines the organization of the endothelial ionic signaling machinery in the most extensively studied human microvascular beds, such as the skin, skeletal muscle, and brain, while also discussing vascular reactivity in vessels isolated ex vivo. Accumulating evidence indicates that a distinct repertoire of endothelial ion channels engages diverse endothelium-dependent vasorelaxant pathways across different vascular beds. Understanding how endothelial channels regulate the microvascular unit is predicted to foster the search for alternative therapeutic strategies for treating cardiovascular and neurodegenerative disorders associated with endothelial dysfunction.
Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in Molecular Pathology, Diagnostics, and Therapeutics)
Open AccessArticle
TRPA1 for Butterfly Eyespot Formation
by
Momo Ozaki and Joji M. Otaki
Int. J. Mol. Sci. 2026, 27(3), 1420; https://doi.org/10.3390/ijms27031420 - 30 Jan 2026
Abstract
Butterfly wing color pattern formation is a process of two-dimensional morphogenesis involving long-range lateral signaling in pupal wing tissues. We hypothesized that TRP (transient receptor potential) channels, which are multimodal sensors for various stimuli, are involved in this developmental process. Using the blue
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Butterfly wing color pattern formation is a process of two-dimensional morphogenesis involving long-range lateral signaling in pupal wing tissues. We hypothesized that TRP (transient receptor potential) channels, which are multimodal sensors for various stimuli, are involved in this developmental process. Using the blue pansy butterfly Junonia orithya, we injected the TRPA1 antagonists, AM0902 and AP-18, and an agonist, JT010, into pupae and observed that the eyespot core disk area in adult wings increased and decreased in response to AM0902 and JT010, respectively, although AP-18 did not induce any change. Furthermore, the eyespot outer black ring area increased in response to AM0902, and the orange ring area increased in response to JT010. We detected TRPA1 mRNA via RT‒PCR in the pupal wing tissues of this species. An antibody against the J. orithya TRPA1 extracellular site induced unique aberrant color patterns with wing vein defects. These results suggest that TRPA1 is expressed in pupal wing tissue and may integrate signaling information to determine eyespot size and structure in butterfly wings. TRPA1 likely suppresses the black core disk and the outer black ring and enhances the nonblack orange ring in eyespots during development.
Full article
(This article belongs to the Special Issue Selected Papers from the 5th International Symposium on Frontiers in Molecular Science (ISFMS))
Open AccessReview
The Transplantation of Pancreatic Islets to Portal Vein: The Influence on Liver Tissue
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Alžběta Vojtíšková, Eva Fábryová, Zuzana Berková, Tomas Koblas, Peter Girman and Jan Kříž
Int. J. Mol. Sci. 2026, 27(3), 1419; https://doi.org/10.3390/ijms27031419 - 30 Jan 2026
Abstract
Pancreatic islet (PI) transplantation (Tx) to the portal vein is an established therapeutic modality for selected type 1 diabetic patients. However, a comprehensive review considering the effects of PIs on surrounding liver tissue is lacking. Typical interactions can be detected in the early
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Pancreatic islet (PI) transplantation (Tx) to the portal vein is an established therapeutic modality for selected type 1 diabetic patients. However, a comprehensive review considering the effects of PIs on surrounding liver tissue is lacking. Typical interactions can be detected in the early and delayed phases. This review summarizes known side effects of PI transplantation. In early phase the interaction occurs immediately upon contact of the PI into portal vein blood. Mechanical obstruction, exacerbated by thrombosis as part of the instant blood-mediated inflammatory reaction (IBMIR), leads to ischemic injury to adjacent liver tissue. Delayed changes, such as focal steatosis and glycogen accumulation appear days to weeks after Tx and are caused by local overstimulation of hepatocytes by insulin in supraphysiological concentrations. In animal models these lesions could progress over months to cystic cholangiomas or hepatocellular carcinomas. Such neoplastic changes have been observed in experimental animals; they have not been reported in human patients. In conclusion, while PITx into the liver is not an optimal procedure, it currently represents the site offering the best functional integration of the graft. The adverse effects discussed are pronounced but generally not severe, nor do they appear to compromise the overall health status of the recipients.
Full article
(This article belongs to the Special Issue Pancreatic Disease: From Molecular Basis to Novel Therapies—2nd Edition)
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Open AccessReview
A Translational Roadmap for Neurological Nonsense Mutation Disorders
by
Jiaqing Li, Zhenyun Zhu and Sanqing Xu
Int. J. Mol. Sci. 2026, 27(3), 1418; https://doi.org/10.3390/ijms27031418 - 30 Jan 2026
Abstract
Nonsense mutations, responsible for ~11% of gene lesions causing human monogenic diseases, introduce premature termination codons (PTCs) that lead to truncated proteins and nonsense-mediated mRNA decay (NMD). In the central nervous system (CNS), these mutations drive severe, progressive neurological conditions such as spinal
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Nonsense mutations, responsible for ~11% of gene lesions causing human monogenic diseases, introduce premature termination codons (PTCs) that lead to truncated proteins and nonsense-mediated mRNA decay (NMD). In the central nervous system (CNS), these mutations drive severe, progressive neurological conditions such as spinal muscular atrophy, Rett syndrome, and Duchenne muscular dystrophy. Readthrough therapies—strategies to override PTCs and restore full-length protein expression—have evolved from early aminoglycosides to modern precision tools including suppressor tRNAs, RNA editing, and CRISPR-based platforms. Yet clinical translation remains hampered by inefficient CNS delivery, variable efficacy, and the absence of personalized stratification. In this review, we propose a translational framework—the 4 Ds of Readthrough Therapy—to systematically address these barriers. The framework dissects the pipeline into Detection (precision patient identification and biomarker profiling), Delivery (engineered vectors for CNS targeting), Decoding (context-aware molecular correction), and Durability (long-term safety and efficacy). By integrating advances in machine learning, nanocarriers, base editing, and adaptive trial designs, this roadmap provides a structured strategy to bridge the translational gap. We advocate that a synergistic, modality-tailored approach will transform nonsense suppression from palliative care to durable, precision-based cures for once-untreatable neurological disorders.
Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in Molecular Genetics and Genomics)
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Open AccessReview
Audiovestibular Dysfunction Related to Long COVID-19 Syndrome: A Systematic Review of Characteristics, Pathophysiology, Diagnosis, and Management
by
Jiann-Jy Chen, Chih-Wei Hsu, Hung-Yu Wang, Brendon Stubbs, Tien-Yu Chen, Chih-Sung Liang, Yen-Wen Chen, Bing-Syuan Zeng and Ping-Tao Tseng
Int. J. Mol. Sci. 2026, 27(3), 1417; https://doi.org/10.3390/ijms27031417 - 30 Jan 2026
Abstract
Long COVID-19 syndrome (or so-called post-COVID-19) is indicated by miscellaneous symptoms, usually starting 3 months from the COVID-19 infection and lasting for at least 2 months, which cannot be explained by an alternative diagnosis. There has been more and more reports addressing the
[...] Read more.
Long COVID-19 syndrome (or so-called post-COVID-19) is indicated by miscellaneous symptoms, usually starting 3 months from the COVID-19 infection and lasting for at least 2 months, which cannot be explained by an alternative diagnosis. There has been more and more reports addressing the audiovestibular dysfunction related to long COVID-19 syndrome. Emerging evidence suggests that the linkage between audiovestibular dysfunction and long COVID-19 syndrome might rely on (a) direct inner ear system damage related to viral invasion and consequent inflammation, (b) micro thromboembolic events, which might result from the COVID-19-induced autoimmune reaction against endothelial cells, and consequent transient-ischemia and hypoxia of the auditory pathways, (c) the disturbed nerve conduction in vestibulocochlear nerves due to viral invasion, and finally (d) altered auditory cortex function, either imbalanced central gain or neurotransmitter disturbance. However, most of the aforementioned mechanism remained hypothetic and still needed further studies to approve or refute. This systematic review synthesizes current evidence on the characteristics, pathophysiology, diagnostic approaches, and management of audiovestibular dysfunction related to long COVID-19 syndrome. Literature searches across PubMed, Embase, ClinicalKey, Web of Science, and ScienceDirect (up to 15 December 2025) were conducted in accordance with PRISMA guidelines. Through this systematic review, we provided a schematic diagram of the physiopathology of long COVID-19 syndrome-related audiovestibular dysfunction. Further, we summarized the currently available diagnostic tools to explore the audiovestibular function in such patients. The currently available treatment, either pharmacotherapy or nonpharmacotherapy, mainly tackles idiopathic audiovestibular dysfunction but not specifically long COVID-19 syndrome-related audiovestibular dysfunction. Timely recognition and intervention may prevent progression to permanent hearing loss or vestibular disability, improving quality of life. Trial registration: PROSPERO CRD420251265741.
Full article
(This article belongs to the Special Issue Recent Advances in Pathophysiology and Immunology Related to SARS-CoV-2 Infection)
Open AccessArticle
Sublethal Antibiotic Exposure Induces Microevolution of Quinolone Resistance in Pathogenic Vibrio parahaemolyticus
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Qian Wu, Han Yang, Tianming Xu, Pradeep K. Malakar, Huan Li and Yong Zhao
Int. J. Mol. Sci. 2026, 27(3), 1416; https://doi.org/10.3390/ijms27031416 - 30 Jan 2026
Abstract
The microevolutionary pathways and molecular mechanisms by which the important pathogen Vibrio parahaemolyticus acquires resistance in the aquatic environment under continuous selective pressure from quinolone antibiotic residues are still unknown. Here, the study successfully simulated the long-term pressure of antibiotic residues in aquaculture
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The microevolutionary pathways and molecular mechanisms by which the important pathogen Vibrio parahaemolyticus acquires resistance in the aquatic environment under continuous selective pressure from quinolone antibiotic residues are still unknown. Here, the study successfully simulated the long-term pressure of antibiotic residues in aquaculture by susceptible V. parahaemolyticus (VPD14) which was isolated from seafood, to a 30-day in vitro induction with sublethal concentrations of levofloxacin, which yielded the mutants (VPD14M). A phenotypic analysis revealed that VPD14M exhibited resistance to ampicillin, levofloxacin and ciprofloxacin, compared to VPD14. These changes were accompanied by adaptations, including a decreased growth rate and an enhanced biofilm formation capacity. Whole-Genome Sequencing identified that the acquired resistance was primarily attributable to key point mutations in three Quinolone Resistance-Determining Regions (QRDRs). Specifically, a G → T substitution at nucleotide position 248 in the gyrA gene, leading to a serine-to-isoleucine substitution at the 83rd amino acid position (Ser83Ile) of the DNA gyrase subunit A; a C → T substitution at position 254 in the parC gene, resulting in a serine-to-phenylalanine substitution at position 85 (Ser85Phe) of the topoisomerase IV subunit A; and a C → T substitution at position 2242 in the gyrB gene, causing a proline-to-serine substitution at position 748 (Pro748Ser) of the DNA gyrase subunit B. Collectively, the study demonstrated that sublethal antibiotic levels rapidly drive quinolone resistance in V. parahaemolyticus, and the specific mutations identified offer critical support for resistance monitoring and seafood safety alerts.
Full article
(This article belongs to the Special Issue Advanced Strategies in Bacterial Antibiotic Resistance)
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Antidiabetic Effects of Anthocyanins on Pancreatic β-Cell Function: A Systematic Review of In Vitro Studies
by
Ravish Kumkum, Theresha Ruwan Pathiranage, Bryony A. McNeill, Leni R. Rivera and Kathryn Aston-Mourney
Int. J. Mol. Sci. 2026, 27(3), 1415; https://doi.org/10.3390/ijms27031415 - 30 Jan 2026
Abstract
Pancreatic β-cell dysfunction is the key driver of type 2 diabetes, and anthocyanins have been proposed as dietary compounds that may help preserve β-cell health. This systematic review aimed to synthesise evidence on the direct effects of anthocyanins on β-cell viability, apoptosis, oxidative
[...] Read more.
Pancreatic β-cell dysfunction is the key driver of type 2 diabetes, and anthocyanins have been proposed as dietary compounds that may help preserve β-cell health. This systematic review aimed to synthesise evidence on the direct effects of anthocyanins on β-cell viability, apoptosis, oxidative stress, and insulin secretion across in vitro models. Four databases were searched in March–April 2025, and eighteen studies met the inclusion criteria. Purified anthocyanins—including cyanidin-3-glucoside (C3G), cyanidin-3-rutinoside (C3R), malvidin-3-glucoside (M3G), and delphinidin-3-glucoside (D3G)—as well as anthocyanin-rich berry extracts, were tested in INS-1, MIN6, RIN-m5F cells and primary mouse or human islets under glucotoxic, lipotoxic, oxidative, cytokine, and amyloidogenic stress. Anthocyanins consistently improved β-cell viability, reduced apoptosis, and lowered reactive oxygen species (ROS), nitric oxide (NO), and thiobarbituric acid reactive substances (TBARSs) levels while enhancing antioxidant enzyme activities. Multiple studies showed upregulation of insulin secretion-related genes and proteins, and both acute and chronic treatments increased glucose-stimulated insulin secretion under normal and stressed conditions. Mechanistic pathways involved modulation of mitogen-activated protein kinase (MAPK) signalling, endoplasmic reticulum (ER) stress responses, inflammatory mediators, and mitophagy (PINK1/PARKIN). While effective in vitro concentrations were higher than typical circulating levels, the collective evidence highlights anthocyanins as promising β-cell protective agents and underscores the need for studies examining their metabolites and physiologically relevant exposure.
Full article
(This article belongs to the Special Issue The Effect of Food-Derived Compounds on Brown Fat Cell Function)
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Open AccessArticle
Flow Cytometry-Based Monitoring of Microbial Dynamics During Grape Must Fermentation Under Different Inoculation Strategies
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Federico Sizzano, Valentina Bianconi, Eddy Dorsaz, Antoine Boilley, Hélène Berthoud, Nadine Bridy, Laurent Amiet and Gilles Bourdin
Int. J. Mol. Sci. 2026, 27(3), 1414; https://doi.org/10.3390/ijms27031414 - 30 Jan 2026
Abstract
We applied flow cytometry (FCM) to monitor microbial dynamics during grape must fermentation at the winery scale. Experiments were performed on Pinot Noir grapes using three distinct winemaking protocols: inoculation with active dried yeast, Pied-de-Cuve, and spontaneous fermentation. FCM enabled the assessment
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We applied flow cytometry (FCM) to monitor microbial dynamics during grape must fermentation at the winery scale. Experiments were performed on Pinot Noir grapes using three distinct winemaking protocols: inoculation with active dried yeast, Pied-de-Cuve, and spontaneous fermentation. FCM enabled the assessment of yeast viability and metabolic activity, as well as the detection and monitoring of viable bacterial populations during alcoholic fermentation. Amplicon-based DNA sequencing was performed to characterize the associated microbial communities and evaluate protocol-specific effects. Trends identified by amplicon sequencing were partially mirrored by patterns observed in unsupervised FCM analysis. Overall, our results indicate that FCM is a practical tool for monitoring microbial dynamics during fermentation, providing near–real-time information that can support monitoring strategies and risk management in winemaking.
Full article
(This article belongs to the Special Issue Flow Cytometry: Applications and Challenges)
Open AccessArticle
Investigations of Diclofenac Sorption on Intact and Modified Chlorella vulgaris Biomass with pH-Switchable Desorption
by
Ivan Liakh, Adrian Szewczyk, Magdalena Prokopowicz, Magdalena Narajczyk, Anna Aksmann, Darya Harshkova and Bartosz Wielgomas
Int. J. Mol. Sci. 2026, 27(3), 1413; https://doi.org/10.3390/ijms27031413 - 30 Jan 2026
Abstract
The growing interest in sustainable and structurally diverse sorbent materials has intensified the search for effective biosorbents that can complement or replace conventional adsorbents. This work presents the potential use of Chlorella vulgaris dried biomass and its modifications (ultrasound-treated, lipid-extracted, and combined forms)
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The growing interest in sustainable and structurally diverse sorbent materials has intensified the search for effective biosorbents that can complement or replace conventional adsorbents. This work presents the potential use of Chlorella vulgaris dried biomass and its modifications (ultrasound-treated, lipid-extracted, and combined forms) for diclofenac (DCF) sorption from aqueous solutions. It was demonstrated that sorption efficiency significantly depends on the solution’s pH. Lowering the pH from 6 to 2 increases the sorption from 5% to 68%, while 99% desorption occurred at pH 9. The adsorption isotherms for intact biomass and after lipid extraction (CV-E2) are best described by the Langmuir and Freundlich models; for ultrasonically treated biomass (CV-E1) by the Temkin model; and for ultrasound-assisted solvent extraction (CV-E3) by the Dubinin–Radushkevich model. These findings demonstrate that cellular lipids and particle characteristics critically govern sorption mechanisms, highlighting dried Chlorella biomass as a structurally and chemically tunable biosorbent. Importantly, the key sorption experiments were performed under strongly acidic conditions (pH 2), which differ from typical wastewater or surface water matrices. Therefore, the presented results should be regarded as a proof of concept illustrating the mechanistic potential of dried Chlorella biomass as a tunable sorptive material, with prospective relevance for separation science and laboratory-scale analytical applications rather than direct environmental remediation.
Full article
(This article belongs to the Special Issue Molecular Advances in Adsorbing Materials)
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Open AccessArticle
Molecular Surveillance, Evolution, and Vaccine Strain Match of the HA and NA Genes of 2009 H1N1 Pandemic Virus Circulating in Riyadh, Saudi Arabia
by
Reem M. Aljowaie, Ibrahim M. Aziz, Mohamed A. Farrag, Abdulaziz M. Almuqrin and Fahad N. Almajhdi
Int. J. Mol. Sci. 2026, 27(3), 1412; https://doi.org/10.3390/ijms27031412 - 30 Jan 2026
Abstract
Influenza viruses are characterized by their high mutation rates which require continuous molecular surveillance to ensure the annual effectiveness of influenza vaccines. The current study aimed to investigate the molecular evolution and vaccine match of the 2009 pandemic (A(H1N1) pdm09) virus circulating in
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Influenza viruses are characterized by their high mutation rates which require continuous molecular surveillance to ensure the annual effectiveness of influenza vaccines. The current study aimed to investigate the molecular evolution and vaccine match of the 2009 pandemic (A(H1N1) pdm09) virus circulating in Riyadh, Saudi Arabia. A total of 380 nasopharyngeal aspirates (NPAs) were collected during the 2020–2023 winter seasons from patients with influenza-like illness. Influenza A virus (IAV) detection, typing, and amplification of hemagglutinin (HA) and neuraminidase (NA) genes were achieved using one-step RT-PCR. The full-length HA and NA genes of 14 selected A(H1N1) pdm09 isolates were sequenced and used for sequence and phylogenetic analysis, which also included sequences of seven A(H1N1) pdm09 isolates collected in Riyadh during the 2024–2025 season. IAV was detected in 17.11% samples; A/H3N2 (9.21%) was somewhat more prevalent than A(H1N1) pdm09 (7.89%). Children aged 0–4 years had the highest incidence rate of infection. Comparing the HA1 domain of A(H1N1) pdm09 isolates circulating in Riyadh to the current vaccine strains (A/Wisconsin/67/2022 and A/Victoria/4897/2022), a total of 24 amino acid substitutions were identified. O-linked and N-linked glycosylation sites in the HA and NA proteins of the Riyadh isolates coincided with those of the two vaccine strains. The receptor-binding domain (130-loop) of the HA1 domain showed a persistent S137P substitution in all study isolates; this mutation is not present in the current vaccination strain. This finding suggests a potential antigenic mismatch between the current vaccine and the circulating A(H1N1) pdm09 strains in Riyadh, warranting hemagglutination inhibition (HAI) assays to confirm the impact of the S137P substitution on antigenicity and immune evasion. As shown above, ongoing molecular surveillance is essential for guiding the yearly selection of vaccine candidates to increase efficacy.
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(This article belongs to the Special Issue Influenza Pathogenesis and Vaccine Development)
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Open AccessArticle
Role of Inositol Hexakisphosphate Kinases in Vascular Smooth Muscle Cell Calcification
by
Sheyda Bahiraii, Isratul Jannat, Sarah Plösser, Mehdi Razazian, Jakob Voelkl and Ioana Alesutan
Int. J. Mol. Sci. 2026, 27(3), 1411; https://doi.org/10.3390/ijms27031411 - 30 Jan 2026
Abstract
Phosphate-induced vascular calcification in chronic kidney disease is linked to cardiovascular mortality. This calcification process involves vascular smooth muscle cells (VSMCs), which can promote a pro-calcific environment in the vascular wall. However, the mechanisms underlying a putative phosphate sensing of VSMCs to modulate
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Phosphate-induced vascular calcification in chronic kidney disease is linked to cardiovascular mortality. This calcification process involves vascular smooth muscle cells (VSMCs), which can promote a pro-calcific environment in the vascular wall. However, the mechanisms underlying a putative phosphate sensing of VSMCs to modulate pro-calcific signaling are insufficiently clarified. In mammals, three isoforms of the inositol hexakisphosphate kinase (IP6K) exist, which have been implicated in cellular phosphate homeostasis. Therefore, each IP6K isoform was silenced in calcifying primary human aortic VSMCs. IP6K1 and IP6K2 mRNA expression were increased in calcifying VSMCs. Silencing of either IP6K1 or IP6K2 ameliorated phosphate-induced pro-calcific markers expression and VSMC calcification. IP6K3 mRNA expression was not modified during calcifying conditions, but IP6K3 silencing still resulted in some anti-calcific effects. Mechanistically, the IP6K product 5-IP7 may act as a potent inhibitor of AKT kinase signaling. Accordingly, pro-calcific conditions induced only transient AKT phosphorylation, and IP6K2 silencing increased AKT phosphorylation in calcifying VSMCs. In turn, AKT inhibition blunted the protective effects of IP6K2 knockdown, while serum- and glucocorticoid-inducible kinase 1 (SGK1) inhibition restored these effects. These observations indicate a role for IP6Ks during phosphate-induced VSMC calcification, which could be mediated by an altered balance between AKT and SGK1 signaling.
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(This article belongs to the Special Issue Mechanisms of Vascular Calcification 2.0)
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Open AccessArticle
Molecular Dynamics Insights into Cassia tora-Derived Phytochemicals as Dual Insecticidal and Antifungal Agents Against Tomato Tuta absoluta and Alternaria solani
by
Tijjani Mustapha, Nathaniel Luka Kwarau, Rajesh B. Patil, Huatao Tang, Mai-Abba Ishiyaku Abdullahi, Sheng-Yen Wu and Youming Hou
Int. J. Mol. Sci. 2026, 27(3), 1410; https://doi.org/10.3390/ijms27031410 - 30 Jan 2026
Abstract
The pressing need for sustainable, plant-based alternatives is highlighted by the growing resistance of agricultural pests to synthetic pesticides. This study examined the pesticidal potential of phytocompounds from C. tora discovered by GC–MS analysis against important tomato insect (T. absoluta) and
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The pressing need for sustainable, plant-based alternatives is highlighted by the growing resistance of agricultural pests to synthetic pesticides. This study examined the pesticidal potential of phytocompounds from C. tora discovered by GC–MS analysis against important tomato insect (T. absoluta) and fungal pathogen (A. solani). The binding stability and interaction dynamics of specific metabolites with fungal virulence (polygalacturonase, MAP kinase HOG1, and effector AsCEP50) and insect neuromuscular (ryanodine receptor and sodium channel protein) targets were assessed using molecular docking and 100 ns molecular dynamics simulations. Among the screened compounds, squalene and 4,7,10,13,16,19-docosahexaenoic acid, methyl ester (DHAME) exhibited the strongest binding affinities and conformational stability, with MM-GBSA binding free energies of −38.09 kcal·mol−1 and −52.81 kcal·mol−1 for squalene complexes in T. absoluta and A. solani, respectively. Persistent hydrophobic and mixed hydrophobic–polar contacts that stabilised active-site residues and limited protein flexibility were found by ProLIF analysis. These lively and dynamic profiles imply that DHAME and squalene may interfere with calcium signalling and stress-response pathways, which are essential for the survival and pathogenicity of pests. Hydrophobic interactions were further confirmed as the primary stabilising force by the preponderance of van der Waals and nonpolar solvation energies. The findings show that C. tora metabolites, especially squalene and DHAME, are promising environmentally friendly biopesticide candidates that have both insecticidal and antifungal properties. Their development as sustainable substitutes in integrated pest management systems are supported by their stability, binding efficacy and predicted biosafety.
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(This article belongs to the Special Issue Molecular Strategies for the Discovery, Optimization, and Efficient Use of Green Pesticides)
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Open AccessReview
Orforglipron: A Comprehensive Review of an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity and Type 2 Diabetes
by
Urna Kansakar, Stanislovas S. Jankauskas, Shivangi Pande, Pasquale Mone, Fahimeh Varzideh and Gaetano Santulli
Int. J. Mol. Sci. 2026, 27(3), 1409; https://doi.org/10.3390/ijms27031409 - 30 Jan 2026
Abstract
Orforglipron (LY3502970) is a novel, orally available, nonpeptide glucagon-like peptide-1 receptor agonist (GLP-1 RA) designed to replicate the efficacy of injectable GLP-1 RAs for glycemic control and weight reduction while improving convenience and adherence. Preclinical studies have demonstrated potent receptor engagement, favorable pharmacokinetics,
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Orforglipron (LY3502970) is a novel, orally available, nonpeptide glucagon-like peptide-1 receptor agonist (GLP-1 RA) designed to replicate the efficacy of injectable GLP-1 RAs for glycemic control and weight reduction while improving convenience and adherence. Preclinical studies have demonstrated potent receptor engagement, favorable pharmacokinetics, and central nervous system activity. Phase 1–3 clinical trials have shown significant reductions in glycated hemoglobin (HbA1c), fasting and postprandial glucose, body weight, and cardiovascular risk biomarkers, with an acceptable safety profile. This comprehensive review integrates pharmacological, clinical, and mechanistic evidence, critically evaluates the data, identifies knowledge gaps, and outlines future directions for orforglipron in the treatment of type 2 diabetes and obesity.
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(This article belongs to the Special Issue Molecular Diagnosis and Treatments of Diabetes Mellitus: 2nd Edition)
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Open AccessArticle
Inducible Costimulator and Its Ligand Promote Proliferation and Migration of Tumor Cells in Cutaneous T-Cell Lymphoma
by
Kenta Oka, Takuya Miyagawa, Hiromichi Morita, Hiraku Suga, Tomomitsu Miyagaki, Sayaka Shibata, Hiroaki Kamijo, Yuka Mizuno, Teruyoshi Hisamoto, Issei Omori, Hikari Boki, Tomonori Oka, Naomi Takahashi-Shishido, Makoto Sugaya and Shinichi Sato
Int. J. Mol. Sci. 2026, 27(3), 1408; https://doi.org/10.3390/ijms27031408 - 30 Jan 2026
Abstract
Inducible costimulator (ICOS) is a costimulatory immune checkpoint receptor expressed on activated T-cells, while the ICOS ligand (ICOSL) is expressed on antigen-presenting cells. The ICOS–ICOSL axis promotes the survival of memory and effector T-cells and induces several immune responses. In addition, the ICOS–ICOSL
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Inducible costimulator (ICOS) is a costimulatory immune checkpoint receptor expressed on activated T-cells, while the ICOS ligand (ICOSL) is expressed on antigen-presenting cells. The ICOS–ICOSL axis promotes the survival of memory and effector T-cells and induces several immune responses. In addition, the ICOS–ICOSL interaction induces cell proliferation, cell survival, and cytokine production. The roles of ICOS and ICOSL in cutaneous T-cell lymphoma (CTCL) are unclear. In this study, we examined the roles of ICOS and ICOSL in CTCL. The tumor cells co-expressed ICOS and ICOSL, and the upregulated expression of ICOS and ICOSL reflected disease severity. Anti-ICOS and anti-ICOSL neutralizing antibodies inhibited both the in vitro and in vivo proliferation of CTCL cell lines. The anti-ICOSL neutralizing antibodies induced apoptosis and suppressed CCR4 expression on tumor cells, inhibiting CCR4–CCL17-mediated migration. These results suggest that the ICOS–ICOSL axis plays an essential role in CTCL pathogenesis, and targeting the ICOS–ICOSL axis could be a viable strategy for treating CTCL.
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(This article belongs to the Special Issue Cutaneous Biology, Molecular Dermatology and Dermatopathology, 2nd Edition)
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Open AccessArticle
Biotransformation of Aliphatic and Aromatic Hydrocarbons by Aerobic Bacterial Strains Isolated from Brown Coal
by
Paulina Supel, Katarzyna Starzec, Piotr Kapusta, Joanna Brzeszcz and Paweł Kaszycki
Int. J. Mol. Sci. 2026, 27(3), 1407; https://doi.org/10.3390/ijms27031407 - 30 Jan 2026
Abstract
Lignite collected from a brown coal deposit was colonized with fully aerobic bacteria exhibiting hydrocarbon biodegradation pathways. Six autochthonous strains were isolated and tested for tolerance and biotransformation potential towards various xenobiotics such as hexadecane, squalane, pristane, benzoic acid, naphthalene, phenanthrene, and diesel
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Lignite collected from a brown coal deposit was colonized with fully aerobic bacteria exhibiting hydrocarbon biodegradation pathways. Six autochthonous strains were isolated and tested for tolerance and biotransformation potential towards various xenobiotics such as hexadecane, squalane, pristane, benzoic acid, naphthalene, phenanthrene, and diesel oil. After preliminary screening, four xenobiotic-resistant strains were selected (Rhodococcus opacus CUP11, Pseudomonas fluorescens CUP15, Sphingobacterium sp. CUP16, and Rhodococcus sp. CUP17) and further treated for 14 days under aerobic conditions with variant concentrations of each compound (1, 2.5, 5 and 10 g/dm3). Microbial population dynamics and xenobiotic level changes were monitored. Rhodococcus opacus CUP11 and Rhodococcus sp. CUP17 were the most metabolically versatile bacteria capable of biotransforming several xenobiotics. Among the best-performing strains, the highest degradation yields were obtained for CUP17 (81% removal of diesel oil applied at 10 g/dm3, 99% of 2.5 g/dm3 hexadecane and 27% of 1 g/dm3 squalane), and CUP11 (49% of 10 g/dm3 hexadecane and 48% of 1 g/dm3 pristane). The strain CUP16 utilized squalane (33% at 1 g/dm3). The results suggest that the lignite-indigenous bacteria may be applicable for bioremediation of persistent xenobiotics in environmental cleanup projects.
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(This article belongs to the Special Issue Molecular Research and Utilization of Environmental Microbial Resources)
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