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Exploring the Landscape of Pre- and Post-Synaptic Pediatric Disorders with Epilepsy: A Narrative Review on Molecular Mechanisms Involved
Regulation of Mitochondrial and Peroxisomal Metabolism in Female Obesity and Type 2 Diabetes
Interplay of Cellular Nrf2/NF-κB Signalling after Plasma Stimulation of Malignant vs. Non-Malignant Dermal Cells
The Role of Macrophages in Hepatocellular Carcinoma and Their Therapeutic Potential
C3a Mediates Endothelial Barrier Disruption in Brain-Derived, but Not Retinal, Human Endothelial Cells

Journal Description

International Journal of Molecular Sciences

International Journal of Molecular Sciences is an international, peer-reviewed, open access journal providing an advanced forum for biochemistry, molecular and cell biology, molecular biophysics, molecular medicine, and all aspects of molecular research in chemistry, and is published semimonthly online by MDPI. The Australian Society of Plant Scientists (ASPS), Epigenetics Society, European Calcium Society (ECS), European Chitin Society (EUCHIS), Spanish Society for Cell Biology (SEBC) and others are affiliated with IJMS and their members receive a discount on the article processing charges.

Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, MEDLINE, Embase, CAPlus / SciFinder, and other databases.
Journal Rank: JCR - Q1 (Biochemistry and Molecular Biology) / CiteScore - Q1 (Inorganic Chemistry)
Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 16.8 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the second half of 2024).
Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Testimonials: See what our editors and authors say about the IJMS.
Companion journals for IJMS include: Biophysica, Stresses, Lymphatics and SynBio.

Impact Factor: 4.9 (2023); 5-Year Impact Factor: 5.6 (2023)

Imprint Information Journal Flyer Open Access ISSN: 1422-0067

Latest Articles

25 pages, 2703 KiB

Open AccessReview

Advances and Future Trends in Nanozyme-Based SERS Sensors for Food Safety, Environmental and Biomedical Applications

by Xingyu Wang, Xuemei Tang, Chengzhen Ji, Long Wu and Yongheng Zhu

Int. J. Mol. Sci. 2025, 26(2), 709; https://doi.org/10.3390/ijms26020709 (registering DOI) - 15 Jan 2025

Nanozymes, a kind of nanoparticles with enzyme-mimicking activities, have attracted considerable attention due to their robust catalytic properties, ease of preparation, and resistance to harsh conditions. By combining nanozymes with surface-enhanced Raman spectroscopy (SERS) technology, highly sensitive and selective sensors have been developed. [...] Read more.

Nanozymes, a kind of nanoparticles with enzyme-mimicking activities, have attracted considerable attention due to their robust catalytic properties, ease of preparation, and resistance to harsh conditions. By combining nanozymes with surface-enhanced Raman spectroscopy (SERS) technology, highly sensitive and selective sensors have been developed. These sensors are capable of detecting a wide range of analytes, such as foodborne toxins, environmental pollutants, and biomedical markers. This review provides an overview of recent advancements in the synthesis and surface modification of nanozymes, highlighting their ability to mimic multiple enzymes and enhance catalytic performance. In addition, we explore the development and applications of nanozyme-based SERS sensors in food contaminants, environmental pollutants, and biomedical markers. The review concludes with perspectives and challenges facing the field, involving the need for deeper understanding of nanozyme principles and mechanisms, development of standardized systems for characterization, and the engineering of nanozymes with tailored properties for specific applications. Finally, we discuss the potential for integrating various techniques with nanozymes to create multi-modal detection platforms, paving the way for the next generation of analytical tools in the fields of food safety, environmental monitoring, and biomedical diagnostics. Full article

(This article belongs to the Special Issue Cutting-Edge Research on Nanosensors and Microsensors)

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15 pages, 4183 KiB

Open AccessArticle

A Lateral Line Specific Mucin Involved in Cupula Growth and Vibration Detection in Zebrafish

by Ziyue Ma, Yixuan Tian, Yingying Wang, Chenghao Wang, Jian Wang and Chunxin Fan

Int. J. Mol. Sci. 2025, 26(2), 708; https://doi.org/10.3390/ijms26020708 - 15 Jan 2025

The lateral line system in fish is crucial for detecting water flow, which facilitates various behaviors such as prey detection, predator avoidance, and rheotaxis. The cupula, a gelatinous structure overlaying the hair cells in neuromasts, plays a key role in transmitting mechanical stimuli [...] Read more.

The lateral line system in fish is crucial for detecting water flow, which facilitates various behaviors such as prey detection, predator avoidance, and rheotaxis. The cupula, a gelatinous structure overlaying the hair cells in neuromasts, plays a key role in transmitting mechanical stimuli to hair cells. However, the molecular composition of the cupula matrix remains poorly understood. In this study, we found that Mucin-5AC, a novel family of mucin proteins, composed of 2–27 cysteine-rich domains, presents in cartilaginous and bony fishes. Using in situ hybridization and transgenic reporter assays, we demonstrated that zebrafish muc5AC is specifically expressed in the support cells of neuromasts. Knockdown of muc5AC via antisense morpholino resulted in shorter cupulae in zebrafish lateral line. Additionally, we generated zebrafish muc5AC mutants using CRISPR/Cas9 and found that cupulae in muc5AC mutants were significantly shorter than that in wild-types, but the hair cell number in neuromasts was not changed obviously. Furthermore, muc5AC mutant zebrafish larvae displayed compromised sensitivity to vibration stimuli compared to wild-type larvae. This study provides the first evidence linking the muc5AC gene to cupula development and vibration detection in zebrafish. Our findings suggest that Mucin-5AC is likely a critical component of the cupula matrix, offering an important clue to the molecular composition of the lateral line cupula in fish. Full article

(This article belongs to the Section Molecular Biology)

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14 pages, 677 KiB

Open AccessArticle

A Real-Time PCR Assay for Detecting Codling Moth Cydia pomonella on Material Intercepted at U.S. Ports of Entry—A Valuable Tool for Specimen Identification

by Alicia E. Timm, Luke R. Tembrock, Frida A. Zink and Kayla A. Mollet

Int. J. Mol. Sci. 2025, 26(2), 707; https://doi.org/10.3390/ijms26020707 - 15 Jan 2025

Codling moth Cydia pomonella is well established nearly everywhere apples are grown. Due to this almost global distribution, larvae are often intercepted at U.S. ports of entry where immature specimens cannot be identified accurately to species leading to unnecessary quarantine actions. To assist [...] Read more.

Codling moth Cydia pomonella is well established nearly everywhere apples are grown. Due to this almost global distribution, larvae are often intercepted at U.S. ports of entry where immature specimens cannot be identified accurately to species leading to unnecessary quarantine actions. To assist with identifying intercepted C. pomonella from port inspections, we developed a probe-based real-time PCR assay to amplify the internal transcribed spacer (ITS) region 2 of C. pomonella. The assay was tested for inclusivity using 110 C. pomonella specimens from six continents. Analytical specificity was examined by testing related species intercepted at U.S. ports of entry, as well as non-targets with the same geographic distribution and host species as C. pomonella. The assay developed here identified all C. pomonella individuals correctly and produced appropriately negative results for all non-target species. These results ensure that the assay provides a rapid and accurate tool for unambiguously identifying C. pomonella among material intercepted at U.S. ports of entry. Since C. pomonella is not actionable, the ability to identify all life stages of C. pomonella conclusively will save time, effort, and money while also directing identification efforts towards species of current quarantine concern. Full article

(This article belongs to the Special Issue Advances in the Molecular Diagnostics of Agriculture Pathogens and Pests)

26 pages, 4613 KiB

Open AccessArticle

Decoding Codon Bias: The Role of tRNA Modifications in Tissue-Specific Translation

by Daisuke Ando, Sherif Rashad, Thomas J. Begley, Hidenori Endo, Masashi Aoki, Peter C. Dedon and Kuniyasu Niizuma

Int. J. Mol. Sci. 2025, 26(2), 706; https://doi.org/10.3390/ijms26020706 - 15 Jan 2025

The tRNA epitranscriptome has been recognized as an important player in mRNA translation regulation. Our knowledge of the role of the tRNA epitranscriptome in fine-tuning translation via codon decoding at tissue or cell levels remains incomplete. We analyzed tRNA expression and modifications as [...] Read more.

The tRNA epitranscriptome has been recognized as an important player in mRNA translation regulation. Our knowledge of the role of the tRNA epitranscriptome in fine-tuning translation via codon decoding at tissue or cell levels remains incomplete. We analyzed tRNA expression and modifications as well as codon optimality across seven mouse tissues. Our analysis revealed distinct enrichment patterns of tRNA modifications in different tissues. Queuosine (Q) tRNA modification was most enriched in the brain compared to other tissues, while mitochondrial tRNA modifications and tRNA expression were highest in the heart. Using this observation, we synthesized, and delivered in vivo, codon-mutated EGFP for Q-codons, where the C-ending Q-codons were replaced with U-ending codons. The protein levels of mutant EGFP were downregulated in liver, which is poor in Q, while in brain EGFP, levels did not change. These data show that understanding tRNA modification enrichments across tissues is not only essential for understanding codon decoding and bias but can also be utilized for optimizing gene and mRNA therapeutics to be more tissue-, cell-, or condition-specific. Full article

(This article belongs to the Special Issue Advanced Research of tRNA)

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16 pages, 1441 KiB

Open AccessArticle

Acute Severe Hypoxia Decreases Mitochondrial Chain Complex II Respiration in Human Peripheral Blood Mononuclear Cells

by Marianne Riou, Anne-Laure Charles, Irina Enache, Charles Evrard, Cristina Pistea, Margherita Giannini, Anne Charloux and Bernard Geny

Int. J. Mol. Sci. 2025, 26(2), 705; https://doi.org/10.3390/ijms26020705 - 15 Jan 2025

Peripheral blood mononuclear cells’ (PBMCs) mitochondrial respiration is impaired and likely involved in myocardial injury and heart failure pathophysiology, but its response to acute and severe hypoxia, often associated with such diseases, is largely unknown in humans. We therefore determined the effects of [...] Read more.

Peripheral blood mononuclear cells’ (PBMCs) mitochondrial respiration is impaired and likely involved in myocardial injury and heart failure pathophysiology, but its response to acute and severe hypoxia, often associated with such diseases, is largely unknown in humans. We therefore determined the effects of acute hypoxia on PBMC mitochondrial respiration and ROS production in healthy volunteers exposed to controlled oxygen reduction, achieving an inspired oxygen fraction of 10.5%. We also investigated potential relationships with gene expression of key biomarkers of hypoxia, succinate and inflammation, as hypoxia and inflammation share common mechanisms involved in cardiovascular disease. Unlike global mitochondrial respiration, hypoxemia with a spO₂ ≤ 80% significantly reduced PBMC complex II respiration (from 6.5 ± 1.2 to 3.1 ± 0.5 pmol/s/10⁶ cell, p = 0.04). Complex II activity correlated positively with spO₂ (r = 0.63, p = 0.02) and inversely correlated with the succinate receptor SUCNR1 (r = −0.68), the alpha-subunit of the hypoxia-inducible factor (HIF-1α, r = −0.61), the chemokine ligand-9 (r = −0.68) and interferon-stimulated gene 15 (r = −0.75). In conclusion, severe hypoxia specifically impairs complex II respiration in association with succinate, inflammation and HIF-1α pathway interactions in human PBMCs. These results support further studies investigating whether modulation of complex II activity might modify the inflammatory and metabolic alterations observed in heart failure. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Pathophysiology of Myocardial Disease)

11 pages, 2895 KiB

Open AccessArticle

Liquid-Based Diagnostic Panels for Prostate Cancer: The Synergistic Role of Soluble PD-L1, PD-1, and mRNA Biomarkers

by Margarita Žvirblė, Ieva Vaicekauskaitė, Žilvinas Survila, Paulius Bosas, Neringa Dobrovolskienė, Agata Mlynska, Rasa Sabaliauskaitė and Vita Pašukonienė

Int. J. Mol. Sci. 2025, 26(2), 704; https://doi.org/10.3390/ijms26020704 - 15 Jan 2025

This study aimed to evaluate the diagnostic potential of soluble Programmed Death Ligand 1 (sPD-L1) and Programmed Death 1 (sPD-1) molecules in plasma, along with urinary mRNA biomarkers—Prostate-Specific Membrane Antigen (PSMA), Prostate Cancer Antigen 3 (PCA3), and androgen receptor [...] Read more.

This study aimed to evaluate the diagnostic potential of soluble Programmed Death Ligand 1 (sPD-L1) and Programmed Death 1 (sPD-1) molecules in plasma, along with urinary mRNA biomarkers—Prostate-Specific Membrane Antigen (PSMA), Prostate Cancer Antigen 3 (PCA3), and androgen receptor (AR) genes—for identifying clinically significant prostate cancer (PCa), defined as pathological stage 3. In a cohort of 68 PCa patients, sPD-L1 and sPD-1 levels were quantified using ELISA, while mRNA transcripts were measured by RT-qPCR. Results highlight the potential of integrating these liquid-based biomarkers. In particular, the combination of sPD-L1, sPD-1, and AR demonstrated the most significant improvement in diagnostic performance, increasing the area under the curve (AUC) from 0.65 to 0.81 and sensitivity from 60% to 88%, compared to AR alone. PSMA demonstrated an AUC of 0.82 and a specificity of 52.8%, which improved to an AUC of 0.85 and a specificity of 94.4% with the inclusion of sPD-L1 and sPD-1. Similarly, PCA3 achieved an AUC of 0.75 and a specificity of 53.8%, increasing to an AUC of 0.78 and a specificity of 76.9% when combined with these biomarkers. Incorporating sPD-L1 into a three-gene panel further elevated the AUC from 0.74 to 0.94. These findings underscore the value of multimodal liquid-based diagnostic panels in improving the management of clinically significant PCa. Full article

(This article belongs to the Special Issue Liquid Biopsies in Oncology II)

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26 pages, 1855 KiB

Open AccessArticle

Effect of a Low-Molecular-Weight Allosteric Agonist of the Thyroid-Stimulating Hormone Receptor on Basal and Thyroliberin-Stimulated Activity of Thyroid System in Diabetic Rats

by Kira V. Derkach, Alena S. Pechalnova, Viktor N. Sorokoumov, Inna I. Zorina, Irina Y. Morina, Elizaveta E. Chernenko, Egor A. Didenko, Irina V. Romanova and Alexander O. Shpakov

Int. J. Mol. Sci. 2025, 26(2), 703; https://doi.org/10.3390/ijms26020703 - 15 Jan 2025

The approaches to correct thyroid deficiency include replacement therapy with thyroid hormones (THs), but such therapy causes a number of side effects. A possible alternative is thyroid-stimulating hormone (TSH) receptor activators, including allosteric agonists. The aim of this work was to study the [...] Read more.

The approaches to correct thyroid deficiency include replacement therapy with thyroid hormones (THs), but such therapy causes a number of side effects. A possible alternative is thyroid-stimulating hormone (TSH) receptor activators, including allosteric agonists. The aim of this work was to study the effect of ethyl-2-(4-(4-(5-amino-6-(tert-butylcarbamoyl)-2-(methylthio)thieno[2,3-d]pyrimidin-4-yl)phenyl)-1H-1,2,3-triazol-1-yl) acetate (TPY3m), a TSH receptor allosteric agonist developed by us, on basal and thyroliberin (TRH)-stimulated TH levels and the hypothalamic-pituitary-thyroid (HPT) axis in male rats with high-fat diet/low-dose streptozotocin-induced type 2 diabetes mellitus (T2DM). Single and three-day administration of TPY3m (i.p., 20 mg/kg) was studied, and the effect of TPY3m on the HPT axis was compared with that of levothyroxine. TPY3m increased TH levels when administered to both healthy and diabetic rats, normalizing thyroxine and triiodothyronine levels in T2DM and, unlike levothyroxine, without negatively affecting TSH levels or the expression of hypothalamic and pituitary genes responsible for TSH production. TPY3m pretreatment preserved the stimulatory effects of TRH on TH levels and thyroid gene expression. This indicates the absence of competition between TPY3m and endogenous TSH for TSH receptor activation and is supported by our in vitro results on TPY3m- and TSH-stimulated adenylate cyclase activity in rat thyroid membranes. Morphological analysis of thyroid glands in diabetic rats after three-day TPY3m administration shows an increase in its functional activity without destructive changes. To summarize, TPY3m, with the activity of a partial allosteric agonist of the TSH receptor, was created as a prototype of drugs to correct thyroid insufficiency in T2DM. Full article

(This article belongs to the Special Issue Thyroid Hormone and Molecular Endocrinology)

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15 pages, 1289 KiB

Open AccessArticle

Mechanism of Functional Compound Fruit Drinks in Regulating Serum Metabolism in Constipated Mice

by Quanhong Lu, Yali Shi, Xin Wen, Lulu Zhu, Longteng Zhang, Kexue Zhu, Jun Cao and Chuan Li

Int. J. Mol. Sci. 2025, 26(2), 702; https://doi.org/10.3390/ijms26020702 - 15 Jan 2025

A compound fruit drink (CFD) is a functional beverage containing fruits, Chinese herbal medicine, and prebiotic fructose. Previous studies have shown the effect of a CFD on alleviating constipation and its impact on gut microbiota. However, a comprehensive analysis has not been reported [...] Read more.

A compound fruit drink (CFD) is a functional beverage containing fruits, Chinese herbal medicine, and prebiotic fructose. Previous studies have shown the effect of a CFD on alleviating constipation and its impact on gut microbiota. However, a comprehensive analysis has not been reported in regard to the serum metabolism of CFDs. This study established a mouse constipation model, using loperamide hydrochloride. Herein, based on UHPLC–QTOF/MS analysis, 93 differential metabolites (mainly including phosphoglycerides and amino acid derivatives) among the groups of mice were identified. After CFD treatment, the content of phosphatidylethanolamine, amino acid derivatives (including N-Acetyl-L-aspartate, L-Norleucine, and cis-4-Hydroxy-D-proline), and fumarate increased, while that of esters decreased. Pathway enrichment analysis revealed that the CFD mitigated constipation by modulating nine metabolic pathways, which encompass glycerophospholipid metabolism, the tricarboxylic acid (TCA) cycle, pyruvate metabolism, and tyrosine metabolism. Notably, the glycerophospholipid metabolic pathway was identified as the most pertinent. Collectively, the results provide new ideas for developing functional foods that nourish the intestines and relieve constipation. Full article

(This article belongs to the Special Issue Multiomics and Functional Foods: Molecular Characterization, Structures and Biological Activities)

19 pages, 1888 KiB

Open AccessArticle

Ac/Ds-like Transposon Elements Inserted in ZmABCG2a Cause Male Sterility in Maize

by Le Wang, Saeed Arshad, Taotao Li, Mengli Wei, Hong Ren, Wei Wang, Haiyan Jia, Zhengqiang Ma and Yuanxin Yan

Int. J. Mol. Sci. 2025, 26(2), 701; https://doi.org/10.3390/ijms26020701 - 15 Jan 2025

Using male sterile (MS) lines instead of normal inbred maternal lines in hybrid seed production can increase the yield and quality with lower production costs. Therefore, developing a new MS germplasm is essential for maize hybrid seed production in the future. Here, we [...] Read more.

Using male sterile (MS) lines instead of normal inbred maternal lines in hybrid seed production can increase the yield and quality with lower production costs. Therefore, developing a new MS germplasm is essential for maize hybrid seed production in the future. Here, we reported a male sterility gene ms*-N125, cloned from a newly found MS mutant ms*-N125. This mutant has an underdeveloped tassel that showed impaired glumes and shriveled anthers without pollen grains. The MS locus of ms*-N125 was mapped precisely to a 112-kb-interval on the chromosome 5. This interval contains only three candidate genes, Zm958, Zm959, and Zm960. Sequencing results showed that only candidate Zm960 harbored a 548-bp transposable element (TE) in its 9th exon, and the two other candidate genes were found to have no genetic variations between the mutant and wild type (WT). Thus, Zm960 is the only candidate gene for male sterility of the mutant ms*-N125. In addition, we screened another recessive MS mutant, ms*-P884, which exhibited similar male sterility phenotypes to ms*-N125. Sequencing Zm960 in ms*-P884 showed a 600-bp TE located in its 2nd exon. Zm960 encodes an ATP-binding cassette in the G subfamily of ABC (ABCG) transporters, ZmABCG2a, with both mutants which harbored an Ac/Ds-like transposon in each. To verify the function of ZmABCG2a for male sterility further, we found an ethyl methanesulfonate (EMS) mutant, zmabcg2a*, which displayed male sterility and tassel phenotypes highly similar to ms*-N125 and ms*-P884, confirming that ZmABCG2a must be the gene for male sterility in maize. In addition, the results of lipid metabolome analysis of ms*-N125 young tassels showed that the total lipid content of the mutant was significantly lower than that of the WT, with 15 subclasses of lipids, including PE (phosphatidylethanolamine), PC (phosphatidylcholine), DG (digalactosyldiacylglycerols), and MGDG (monogalactosyldiacylglycerol) which were significantly down-regulated in the ms*-N125 mutant versus its wild type. In summary, we identified alternate mutations of the ZmABCG2a gene, which may be a potential germplasm for hybrid seed production in maize. Full article

(This article belongs to the Special Issue Molecular Breeding and Genetic Regulation of Crops, 2nd Edition)

18 pages, 4946 KiB

Open AccessArticle

Identifying a Biocontrol Bacterium with Disease-Prevention Potential and Employing It as a Powerful Biocontrol Agent Against Fusarium oxysporum

by Qi Wang, Zhenshu Sun, Tiantian Li, Tiantian Fan, Ziqi Zhou, Jiayin Liu, Xiuling Chen and Aoxue Wang

Int. J. Mol. Sci. 2025, 26(2), 700; https://doi.org/10.3390/ijms26020700 - 15 Jan 2025

Biocontrol microbes are environment friendly and safe for humans and animals. To seek biocontrol microbes effective in suppressing Fusarium oxysporum is important for tomato production. F. oxysporum is a soil-borne pathogen capable of causing wilt in numerous plant species. Therefore, we found a [...] Read more.

Biocontrol microbes are environment friendly and safe for humans and animals. To seek biocontrol microbes effective in suppressing Fusarium oxysporum is important for tomato production. F. oxysporum is a soil-borne pathogen capable of causing wilt in numerous plant species. Therefore, we found a biocontrol bacterium with an excellent control effect from the rhizosphere soil of plant roots. In this work, we focus on two parts of work. The first part is the identification and genomic analysis of the biocontrol bacterium Y-4; the second part is the control efficiency of strain Y-4 on F. oxysporum. For this study, we identified strain Y-4 as Bacillus velezensis. It is an aerobic Gram-positive bacterium that can secrete a variety of extracellular enzymes and siderophores. Strain Y-4 also contains a large number of disease-resistant genes and a gene cluster that forms antibacterial substances. In addition, we found that it significantly inhibited the reproduction of F. oxysporum in a culture dish. In the indoor control effect test, after treatment with strain Y-4 suspension, the disease index of tomato plants decreased significantly. Furthermore, the control efficiency of the plants was 71.88%. At the same time, Y-4 bacterial suspension induced an increase in POD and SOD enzyme activities in tomato leaves, resulting in increased plant resistance. Taken together, strain Y-4 proves to be an effective means of controlling F. oxysporum in tomatoes. Full article

(This article belongs to the Section Molecular Microbiology)

47 pages, 2147 KiB

Open AccessReview

Utilization of Cannabidiol in Post-Organ-Transplant Care

by Sachiko Koyama, Jumar Etkins, Joshua Jun, Matthew Miller, Gerald C. So, Debora L. Gisch and Michael T. Eadon

Int. J. Mol. Sci. 2025, 26(2), 699; https://doi.org/10.3390/ijms26020699 - 15 Jan 2025

Cannabidiol (CBD) is one of the major phytochemical constituents of cannabis, Cannabis sativa, widely recognized for its therapeutic potential. While cannabis has been utilized for medicinal purposes since ancient times, its psychoactive and addictive properties led to its prohibition in 1937, with [...] Read more.

Cannabidiol (CBD) is one of the major phytochemical constituents of cannabis, Cannabis sativa, widely recognized for its therapeutic potential. While cannabis has been utilized for medicinal purposes since ancient times, its psychoactive and addictive properties led to its prohibition in 1937, with only the medical use being reauthorized in 1998. Unlike tetrahydrocannabinol (THC), CBD lacks psychoactive and addictive properties, yet the name that suggests its association with cannabis has significantly contributed to its public visibility. CBD exhibits diverse pharmacological properties, most notably anti-inflammatory effects. Additionally, it interacts with key drug-metabolizing enzyme families, including cytochrome P450 (CYP) and uridine 5′-diphospho-glucuronosyltransferase (UGT), which mediate phase I and phase II metabolism, respectively. By binding to these enzymes, CBD can inhibit the metabolism of co-administered drugs, which can potentially enhance their toxicity or therapeutic effects. Mild to moderate adverse events associated with CBD use have been reported. Advances in chemical formulation techniques have recently enabled strategies to minimize these effects. This review provides an overview of CBD, covering its historical background, recent clinical trials, adverse event profiles, and interactions with molecular targets such as receptors, channels, and enzymes. We particularly emphasize the mechanisms underlying its anti-inflammatory effects and interaction with drugs relevant to organ transplantation. Finally, we explore recent progress in the chemical formulation of CBD in order to enhance its bioavailability, which will enable decreasing the dose to use and increase its safety and efficacy. Full article

(This article belongs to the Special Issue Recent Research of Phytochemicals in Health and Disease)

14 pages, 1067 KiB

Open AccessArticle

Glucagon Can Increase Force of Contraction via Glucagon Receptors in the Isolated Human Atrium

by Joachim Neumann, Franziska Schmidt, Britt Hofmann and Ulrich Gergs

Int. J. Mol. Sci. 2025, 26(2), 698; https://doi.org/10.3390/ijms26020698 - 15 Jan 2025

Glucagon can increase the force of contraction (FOC) in, for example, canine hearts. Currently, whether glucagon can also increase the FOC via cAMP-increasing receptors in the human atrium is controversial discussed. Glucagon alone did not (up to 1 µM) raise the FOC in [...] Read more.

Glucagon can increase the force of contraction (FOC) in, for example, canine hearts. Currently, whether glucagon can also increase the FOC via cAMP-increasing receptors in the human atrium is controversial discussed. Glucagon alone did not (up to 1 µM) raise the FOC in human right atrial preparations (HAP). Only in the additional presence of the phosphodiesterase (PDE) 3 inhibitor cilostamide (1 µM) or 1 nM isoprenaline did glucagon raise the FOC, starting at 1 µM. The positive inotropic effects of glucagon in HAP were attenuated by a glucagon receptor antagonist (1 µM SC203972), but not by 100 nM exendin(9-39), a glucagon-like peptide-1 receptor (GLP-1R) antagonist. Glucagon (in the presence of cilostamide) demonstrated a reduced efficacy in elevating the FOC in HAP when compared with isoprenaline. In contrast to glucagon, exenatide alone, a GLP-1R agonist, starting at 1 nM, increased the FOC and was more potent and effective than glucagon in raising the FOC in HAP. The effects of exenatide on the FOC were attenuated by exendin(9-39). Hence, glucagon and GLP-1R agonists act functionally via different receptors in the human right atrium. Clinically, these data suggest that endogenous or exogenous glucagon can stimulate glucagon receptors in the human atrium, but only in the presence of PDE inhibitors. Full article

(This article belongs to the Section Biochemistry)

16 pages, 3134 KiB

Open AccessArticle

Intermediates of Hydrogen Peroxide-Assisted Photooxidation of Salicylic Acid: Their Degradation Rates and Ecotoxicological Assessment

by Alicja Gackowska, Waldemar Studziński and Alexander Shyichuk

Int. J. Mol. Sci. 2025, 26(2), 697; https://doi.org/10.3390/ijms26020697 - 15 Jan 2025

Accelerated photooxidation of salicylic acid (SA) was performed using UV radiation and hydrogen peroxide. HPLC-MS analysis showed that the primary intermediates are 2,5-dihydroxybenzoic acid, 2,3-dihydroxybenzoic acid, pyrocatechol, and phenol. Deeper oxidation leads to low molecular weight aliphatic acids, such as maleic, fumaric, and [...] Read more.

Accelerated photooxidation of salicylic acid (SA) was performed using UV radiation and hydrogen peroxide. HPLC-MS analysis showed that the primary intermediates are 2,5-dihydroxybenzoic acid, 2,3-dihydroxybenzoic acid, pyrocatechol, and phenol. Deeper oxidation leads to low molecular weight aliphatic acids, such as maleic, fumaric, and glyoxylic. The photooxidation of the main intermediates was carried out in the same conditions. The degradation of SA and its main intermediates follows first-order reaction kinetics. In the case of UV irradiation alone, photodegradation of 2,5-dihydroxybenzoic acid is slightly faster (reaction rate constant is 0.007 min⁻¹) compared to SA (0.0052 min⁻¹). Other products degrade more slowly than SA. Hydrogen peroxide, in concentrations of 1.8–8.8 mM, accelerates the photodegradation of salicylic acid and intermediate products. An ecotoxicological evaluation of SA and the main products was performed using the EPI Suite^TM software. The overall persistence (P_OV) and long-range transport potential (LRTP) of all transformation products were assessed using OECD P_OV and the LRTP screening tool. Salicylic acid and its transformation products have low toxicity. Due to their high solubility, these contaminants can travel considerable distances in the aquatic environment. SA and phenol have LRTP values of 156–190 km. Other products can travel shorter distances (less than 100 km). Full article

(This article belongs to the Collection Feature Papers in Molecular Toxicology)

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20 pages, 677 KiB

Open AccessReview

In Vivo and In Vitro Models of Hepatic Fibrosis for Pharmacodynamic Evaluation and Pathology Exploration

by Yanting Hu, Zhongrui Zhang, Akida Adiham, Hong Li, Jian Gu and Puyang Gong

Int. J. Mol. Sci. 2025, 26(2), 696; https://doi.org/10.3390/ijms26020696 - 15 Jan 2025

Hepatic fibrosis (HF) is an important pathological state in the progression of chronic liver disease to end-stage liver disease and is usually triggered by alcohol, nonalcoholic fatty liver, chronic hepatitis viruses, autoimmune hepatitis (AIH), or cholestatic liver disease. Research on novel therapies has [...] Read more.

Hepatic fibrosis (HF) is an important pathological state in the progression of chronic liver disease to end-stage liver disease and is usually triggered by alcohol, nonalcoholic fatty liver, chronic hepatitis viruses, autoimmune hepatitis (AIH), or cholestatic liver disease. Research on novel therapies has become a hot topic due to the reversibility of HF. Research into the molecular mechanisms of the pathology of HF and potential drug screening relies on reliable and rational biological models, mainly including animals and cells. Hence, a number of modeling approaches have been attempted based on human dietary, pathological, and physiological factors in the development of HF. In this review, classical and novel methods of modeling HF in the last 10 years were collected from electronic databases, including Web of Science, PubMed, ScienceDirect, ResearchGate, Baidu Scholar, and CNKI. Animal models of HF are usually induced by chemical toxicants, special diets, pathogenic microorganisms, surgical operations, and gene editing. The advantages and limitations of hepatic stellate cells (HSCs), organoids, and 3D coculture-based HF modeling methods established in vitro were also proposed and summarized. This information provides a scientific basis for the discovery of the pathological mechanism and treatment of HF. Full article

(This article belongs to the Section Molecular Pharmacology)

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35 pages, 4098 KiB

Open AccessReview

Biomedical Application of MSCs in Corneal Regeneration and Repair

by Maria P. De Miguel, Marta Cadenas-Martin, Martha Stokking and Ana I. Martin-Gonzalez

Int. J. Mol. Sci. 2025, 26(2), 695; https://doi.org/10.3390/ijms26020695 - 15 Jan 2025

The World Health Organization estimates that approximately 285 million people suffer from visual impairments, around 5% of which are caused by corneal pathologies. Currently, the most common clinical treatment consists of a corneal transplant (keratoplasty) from a human donor. However, worldwide demand for [...] Read more.

The World Health Organization estimates that approximately 285 million people suffer from visual impairments, around 5% of which are caused by corneal pathologies. Currently, the most common clinical treatment consists of a corneal transplant (keratoplasty) from a human donor. However, worldwide demand for donor corneas amply exceeds the available supply. Lamellar keratoplasty (transplantation replacement of only one of the three layers of the cornea) is partially solving the problem of cornea undersupply. Obviously, cell therapy applied to every one of these layers will expand current therapeutic options, reducing the cost of ophthalmological interventions and increasing the effectiveness of surgery. Mesenchymal stem cells (MSCs) are adult stem cells with the capacity for self-renewal and differentiation into different cell lineages. They can be obtained from many human tissues, such as bone marrow, umbilical cord, adipose tissue, dental pulp, skin, and cornea. Their ease of collection and advantages over embryonic stem cells or induced pluripotent stem cells make them a very practical source for experimental and potential clinical applications. In this review, we focus on recent advances using MSCs from different sources to replace the damaged cells of the three corneal layers, at both the preclinical and clinical levels for specific corneal diseases. Full article

(This article belongs to the Special Issue Biomedical Applications of Mesenchymal Stem Cells)

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26 pages, 1246 KiB

Open AccessReview

Long Non-Coding RNAs in Malignant Human Brain Tumors: Driving Forces Behind Progression and Therapy

by Dakun Pei, Dandan Zhang, Yan Guo, Hongbo Chang and Hongjuan Cui

Int. J. Mol. Sci. 2025, 26(2), 694; https://doi.org/10.3390/ijms26020694 - 15 Jan 2025

Long non-coding RNAs (lncRNAs) play a pivotal role in regulating gene expression and are critically involved in the progression of malignant brain tumors, including glioblastoma, medulloblastoma, and meningioma. These lncRNAs interact with microRNAs (miRNAs), proteins, and DNA, influencing key processes such as cell [...] Read more.

Long non-coding RNAs (lncRNAs) play a pivotal role in regulating gene expression and are critically involved in the progression of malignant brain tumors, including glioblastoma, medulloblastoma, and meningioma. These lncRNAs interact with microRNAs (miRNAs), proteins, and DNA, influencing key processes such as cell proliferation, migration, and invasion. This review highlights the multifaceted impact of lncRNA dysregulation on tumor progression and underscores their potential as therapeutic targets to enhance the efficacy of chemotherapy, radiotherapy, and immunotherapy. The insights provided offer new directions for advancing basic research and clinical applications in malignant brain tumors. Full article

(This article belongs to the Special Issue Non-coding RNAs' Functionality-Diagnosis and Therapy in Cancer and Other Indications)

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17 pages, 12428 KiB

Open AccessArticle

Olaparib Combined with DDR Inhibitors Effectively Prevents EMT and Affects miRNA Regulation in TP53-Mutated Epithelial Ovarian Cancer Cell Lines

by Patrycja Gralewska, Łukasz Biegała, Arkadiusz Gajek, Izabela Szymczak-Pajor, Agnieszka Marczak, Agnieszka Śliwińska and Aneta Rogalska

Int. J. Mol. Sci. 2025, 26(2), 693; https://doi.org/10.3390/ijms26020693 - 15 Jan 2025

Epithelial ovarian cancer (EOC) remains a leading cause of gynecologic cancer mortality. Despite advances in treatment, metastatic progression and resistance to standard therapies significantly worsen patient outcomes. Epithelial–mesenchymal transition (EMT) is a critical process in metastasis, enabling cancer cells to gain invasive and [...] Read more.

Epithelial ovarian cancer (EOC) remains a leading cause of gynecologic cancer mortality. Despite advances in treatment, metastatic progression and resistance to standard therapies significantly worsen patient outcomes. Epithelial–mesenchymal transition (EMT) is a critical process in metastasis, enabling cancer cells to gain invasive and migratory capabilities, often driven by changing miRNA expression involved in the regulation of pathological processes like drug resistance. Targeted therapies like PARP inhibitors (PARPi) have improved outcomes, particularly in BRCA-mutated and DNA repair-deficient tumors; however, resistance and limited efficacy in advanced stages remain challenges. Recent studies highlight the potential synergy of PARPi with DNA damage response (DDR) inhibitors, such as ATR and CHK1 inhibitors, which disrupt cancer cell survival pathways under stress. This study investigated the combined effects of olaparib with ATR and CHK1 inhibitors (ATRi and CHK1i) on migration, invasion, and EMT-related protein expression and miRNA expression in ovarian cancer cell lines OV-90 and SKOV-3. The results demonstrated enhanced cytotoxicity, inhibition of migration and invasion, and modulation of miRNAs linked to metastasis. These findings suggest that combination therapies targeting DNA repair and cell cycle pathways may offer a novel, more effective approach to managing advanced EOC and reducing metastatic spread. Full article

(This article belongs to the Special Issue Gynecologic Diseases: From Molecular Basis to Therapy)

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27 pages, 3744 KiB

Open AccessArticle

Comparative Efficacy of Melatonin and Brassinolide in Mitigating the Adverse Effects of Cadmium on Wolffia arrhiza

by Magdalena Chmur and Andrzej Bajguz

Int. J. Mol. Sci. 2025, 26(2), 692; https://doi.org/10.3390/ijms26020692 - 15 Jan 2025

Melatonin (MT) and brassinolide (BL) are phytohormones that regulate various physiological processes in plants. This study investigates their effects on Wolffia arrhiza when exposed to cadmium (Cd). Plant hormones were quantified using liquid chromatography-mass spectrometry, while photosynthetic pigments and phytochelatins (PCs) were analyzed [...] Read more.

Melatonin (MT) and brassinolide (BL) are phytohormones that regulate various physiological processes in plants. This study investigates their effects on Wolffia arrhiza when exposed to cadmium (Cd). Plant hormones were quantified using liquid chromatography-mass spectrometry, while photosynthetic pigments and phytochelatins (PCs) were analyzed through high-performance liquid chromatography. Protein, monosaccharide levels, and antioxidant activities were also spectrophotometrically measured. The findings reveal that MT and BL treatment decreased Cd accumulation in W. arrhiza compared to plants only exposed to Cd. MT was particularly effective in reversing Cd-induced growth inhibition and reducing stress markers more significantly than BL. It also enhanced antioxidant activity and maintained higher levels of photosynthetic pigments, proteins, and sugars. Although BL was less effective in these aspects, it promoted greater synthesis of glutathione and PCs in Cd-exposed duckweed. Overall, both MT and BL alleviate the negative impact of Cd on W. arrhiza, confirming their crucial role in supporting plant health under metal stress conditions. Full article

(This article belongs to the Special Issue Metal Stress in Plants, 2nd Edition)

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27 pages, 2257 KiB

Open AccessArticle

Transcriptome and Neuroendocrinome Responses to Environmental Stress in the Model and Pest Insect Spodoptera frugiperda

by Wei Gong, Jan Lubawy, Paweł Marciniak, Guy Smagghe, Małgorzata Słocińska, Dongdong Liu, Tongxian Liu and Shunhua Gui

Int. J. Mol. Sci. 2025, 26(2), 691; https://doi.org/10.3390/ijms26020691 - 15 Jan 2025

The fall armyworm, Spodoptera frugiperda, is one of the most notorious pest insects, causing damage to more than 350 plant species, and is feared worldwide as an invasive pest species since it exhibits high adaptivity against environmental stress. Here, we therefore investigated [...] Read more.

The fall armyworm, Spodoptera frugiperda, is one of the most notorious pest insects, causing damage to more than 350 plant species, and is feared worldwide as an invasive pest species since it exhibits high adaptivity against environmental stress. Here, we therefore investigated its transcriptome responses to four different types of stresses, namely cold, heat, no water and no food. We used brain samples as our interest was in the neuroendocrine responses, while previous studies used whole bodies of larvae or moths. In general, the responses were complex and encompassed a vast array of neuropeptides (NPs) and biogenic amines (BAs). The NPs were mainly involved in ion homeostasis regulation (ITP and ITPL) and metabolic pathways (AKH, ILP), and this was accompanied by changes in BA (DA, OA) biosynthesis. Cold and no-water stress changed the NP gene expression with the same patterns of expression but clearly separated from each other, and the most divergent pattern of expression was shown after no-food stress. In conclusion, our data provide a foundation in an important model and pest insect with candidate NPs and BAs and other marker candidate genes in response to environmental stress, and also potential new targets to manage pest insects. Full article

(This article belongs to the Section Biochemistry)

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12 pages, 5969 KiB

Open AccessArticle

Predaceous and Phytophagous Pentatomidae Insects Exhibit Contrasting Susceptibilities to Imidacloprid

by Hongmei Cheng, Zhen Wang, Xiaoyu Yan, Changjin Lin, Yu Chen, Le Ma, Luyao Fu, Xiaolin Dong and Chenxi Liu

Int. J. Mol. Sci. 2025, 26(2), 690; https://doi.org/10.3390/ijms26020690 - 15 Jan 2025

Imidacloprid, a widely used neonicotinoid insecticide, targets insect pests but also affects natural enemies. However, the effects of neonicotinoid insecticides on closely related insects remain unclear. We evaluated the harmful effects of imidacloprid on the phytophagous Halyomorpha halys and predaceous Arma chinensis. [...] Read more.

Imidacloprid, a widely used neonicotinoid insecticide, targets insect pests but also affects natural enemies. However, the effects of neonicotinoid insecticides on closely related insects remain unclear. We evaluated the harmful effects of imidacloprid on the phytophagous Halyomorpha halys and predaceous Arma chinensis. Bioassays revealed that imidacloprid was more toxic to H. halys than to A. chinensis and more harmful to the males than to the females of the two insects. A. chinensis adults recovered from imidacloprid-induced knockdown, as evidenced by restored respiratory rates, metabolic rates, and locomotion. Surviving A. chinensis showed reduced fecundity, suggesting a trade-off between detoxification and reproduction. Bioinformatics analysis of nicotinic acetylcholine receptors (nAChRs) and molecular docking simulations indicated a lower diversity of the nAChR gene family in A. chinensis than in H. halys, with weaker binding to imidacloprid, consistent with the relatively low toxicity of the insecticide in this species. This might account for the susceptibility differences to imidacloprid between the species. These findings underscore the efficacy of imidacloprid against H. halys and provide insights into the toxicities of neonicotinoids to target and non-target insects. Full article

(This article belongs to the Section Molecular Toxicology)

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