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 & Molecular Biology) / CiteScore - Q1 (Inorganic Chemistry)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 16.3 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 2023).
- 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, Obesities, Stresses and Lymphatics.
Impact Factor:
5.6 (2022);
5-Year Impact Factor:
6.2 (2022)
Latest Articles
Raman Imaging—A Valuable Tool for Tracking Fatty Acid Metabolism—Normal and Cancer Human Colon Single-Cell Study
Int. J. Mol. Sci. 2024, 25(8), 4508; https://doi.org/10.3390/ijms25084508 (registering DOI) - 19 Apr 2024
Abstract
Altered metabolism of lipids is a key factor in many diseases including cancer. Therefore, investigations into the impact of unsaturated and saturated fatty acids (FAs) on human body homeostasis are crucial for understanding the development of lifestyle diseases. In this paper, we focus
[...] Read more.
Altered metabolism of lipids is a key factor in many diseases including cancer. Therefore, investigations into the impact of unsaturated and saturated fatty acids (FAs) on human body homeostasis are crucial for understanding the development of lifestyle diseases. In this paper, we focus on the impact of palmitic (PA), linoleic (LA), and eicosapentaenoic (EPA) acids on human colon normal (CCD-18 Co) and cancer (Caco-2) single cells using Raman imaging and spectroscopy. The label-free nature of Raman imaging allowed us to evaluate FAs dynamics without modifying endogenous cellular metabolism. Thanks to the ability of Raman imaging to visualize single-cell substructures, we have analyzed the changes in chemical composition of endoplasmic reticulum (ER), mitochondria, lipid droplets (LDs), and nucleus upon FA supplementation. Analysis of Raman band intensity ratios typical for lipids, proteins, and nucleic acids (I1656/I1444, I1444/I1256, I1444/I750, I1304/I1256) proved that, using Raman mapping, we can observe the metabolic pathways of FAs in ER, which is responsible for the uptake of exogenous FAs, de novo synthesis, elongation, and desaturation of FAs, in mitochondria responsible for energy production via FA oxidation, in LDs specialized in cellular fat storage, and in the nucleus, where FAs are transported via fatty-acid-binding proteins, biomarkers of human colon cancerogenesis. Analysis for membranes showed that the uptake of FAs effectively changed the chemical composition of this organelle, and the strongest effect was noticed for LA. The spectroscopy studies have been completed using XTT tests, which showed that the addition of LA or EPA for Caco-2 cells decreases their viability with a stronger effect observed for LA and the opposite effect observed for PA. For normal cells, CCD-18 Co supplementation using LA or EPA stimulated cells for growing, while PA had the opposite impact.
Full article
(This article belongs to the Section Physical Chemistry and Chemical Physics)
►
Show Figures
Open AccessArticle
Comprehensive Research on Druggable Proteins: From PSSM to Pre-Trained Language Models
by
Hongkang Chu and Taigang Liu
Int. J. Mol. Sci. 2024, 25(8), 4507; https://doi.org/10.3390/ijms25084507 (registering DOI) - 19 Apr 2024
Abstract
Identification of druggable proteins can greatly reduce the cost of discovering new potential drugs. Traditional experimental approaches to exploring these proteins are often costly, slow, and labor-intensive, making them impractical for large-scale research. In response, recent decades have seen a rise in computational
[...] Read more.
Identification of druggable proteins can greatly reduce the cost of discovering new potential drugs. Traditional experimental approaches to exploring these proteins are often costly, slow, and labor-intensive, making them impractical for large-scale research. In response, recent decades have seen a rise in computational methods. These alternatives support drug discovery by creating advanced predictive models. In this study, we proposed a fast and precise classifier for the identification of druggable proteins using a protein language model (PLM) with fine-tuned evolutionary scale modeling 2 (ESM-2) embeddings, achieving 95.11% accuracy on the benchmark dataset. Furthermore, we made a careful comparison to examine the predictive abilities of ESM-2 embeddings and position-specific scoring matrix (PSSM) features by using the same classifiers. The results suggest that ESM-2 embeddings outperformed PSSM features in terms of accuracy and efficiency. Recognizing the potential of language models, we also developed an end-to-end model based on the generative pre-trained transformers 2 (GPT-2) with modifications. To our knowledge, this is the first time a large language model (LLM) GPT-2 has been deployed for the recognition of druggable proteins. Additionally, a more up-to-date dataset, known as Pharos, was adopted to further validate the performance of the proposed model.
Full article
(This article belongs to the Special Issue Deep Learning in Bioinformatics and Biological Data Analysis)
Open AccessArticle
Controlled Molecular Arrangement of Cinnamic Acid in Layered Double Hydroxide through pi-pi Interaction for Controlled Release
by
Taeho Kim, Seung-Min Paek, Kang-Kyun Wang, Jin Kuen Park, Fabrice Salles and Jae-Min Oh
Int. J. Mol. Sci. 2024, 25(8), 4506; https://doi.org/10.3390/ijms25084506 - 19 Apr 2024
Abstract
Cinnamic acid (CA) was successfully incorporated into Zn-Al layered double hydroxide (LDH) through coprecipitation. The CA moiety was stabilized in the interlayer space through not only electrostatic interaction but also intermolecular π-π interaction. It was noteworthy that the CA arrangement was fairly independent
[...] Read more.
Cinnamic acid (CA) was successfully incorporated into Zn-Al layered double hydroxide (LDH) through coprecipitation. The CA moiety was stabilized in the interlayer space through not only electrostatic interaction but also intermolecular π-π interaction. It was noteworthy that the CA arrangement was fairly independent of the charge density of LDH, showing the important role of the layer–CA and CA-CA interactions in molecular stabilization. Computer simulations using the Monte Carlo method as well as analytical approaches including infrared, UV-vis spectroscopy, and differential scanning calorimetry showed the existence of intermolecular interaction. In order to reinforce molecular stabilization, a neutral derivative of CA, cinnamaldehyde (CAD), was additionally incorporated into LDH. It was clearly shown that CAD played a role as a π-π interaction mediator to enhance the stabilization of CA. The time-dependent release of CA from LDH was first governed by the layer charge density of LDH; however, the existence of CAD provided additional stabilization to the CA arrangement to slow down the release kinetics.
Full article
(This article belongs to the Special Issue Synthesis of Advanced Polymer Materials 2.0)
Open AccessReview
Can Compounds of Natural Origin Be Important in Chemoprevention? Anticancer Properties of Quercetin, Resveratrol, and Curcumin—A Comprehensive Review
by
Elżbieta Cecerska-Heryć, Zofia Wiśniewska, Natalia Serwin, Aleksandra Polikowska, Małgorzata Goszka, Weronika Engwert, Jaśmina Michałów, Maja Pękała, Marta Budkowska, Anna Michalczyk and Barbara Dołęgowska
Int. J. Mol. Sci. 2024, 25(8), 4505; https://doi.org/10.3390/ijms25084505 (registering DOI) - 19 Apr 2024
Abstract
Malignant tumors are the second most common cause of death worldwide. More attention is being paid to the link between the body’s impaired oxidoreductive balance and cancer incidence. Much attention is being paid to polyphenols derived from plants, as one of their properties
[...] Read more.
Malignant tumors are the second most common cause of death worldwide. More attention is being paid to the link between the body’s impaired oxidoreductive balance and cancer incidence. Much attention is being paid to polyphenols derived from plants, as one of their properties is an antioxidant character: the ability to eliminate reactive oxygen and nitrogen species, chelate specific metal ions, modulate signaling pathways affecting inflammation, and raise the level and activity of antioxidant enzymes while lowering those with oxidative effects. The following three compounds, resveratrol, quercetin, and curcumin, are polyphenols modulating multiple molecular targets, or increasing pro-apoptotic protein expression levels and decreasing anti-apoptotic protein expression levels. Experiments conducted in vitro and in vivo on animals and humans suggest using them as chemopreventive agents based on antioxidant properties. The advantage of these natural polyphenols is low toxicity and weak adverse effects at higher doses. However, the compounds discussed are characterized by low bioavailability and solubility, which may make achieving the blood concentrations needed for the desired effect challenging. The solution may lie in derivatives of naturally occurring polyphenols subjected to structural modifications that enhance their beneficial effects or work on implementing new ways of delivering antioxidants that improve their solubility and bioavailability.
Full article
(This article belongs to the Special Issue Anti-inflammatory and Antioxidant Effects of Natural Bioactive Compounds)
►▼
Show Figures
Graphical abstract
Open AccessReview
Periodontitis: A Plausible Modifiable Risk Factor for Neurodegenerative Diseases? A Comprehensive Review
by
Adelina S. Plachokova, Jolijn Gjaltema, Eliza R. C. Hagens, Zahra Hashemi, Tim B. A. Knüppe, Thomas J. M. Kootstra, Anita Visser and Bastiaan R. Bloem
Int. J. Mol. Sci. 2024, 25(8), 4504; https://doi.org/10.3390/ijms25084504 - 19 Apr 2024
Abstract
The aim of this comprehensive review is to summarize recent literature on associations between periodontitis and neurodegenerative diseases, explore the bidirectionality and provide insights into the plausible pathogenesis. For this purpose, systematic reviews and meta-analyses from PubMed, Medline and EMBASE were considered. Out
[...] Read more.
The aim of this comprehensive review is to summarize recent literature on associations between periodontitis and neurodegenerative diseases, explore the bidirectionality and provide insights into the plausible pathogenesis. For this purpose, systematic reviews and meta-analyses from PubMed, Medline and EMBASE were considered. Out of 33 retrieved papers, 6 articles complying with the inclusion criteria were selected and discussed. Additional relevant papers for bidirectionality and pathogenesis were included. Results show an association between periodontitis and Alzheimer’s disease, with odds ratios of 3 to 5. A bidirectional relationship is suspected. For Parkinson’s disease (PD), current evidence for an association appears to be weak, although poor oral health and PD seem to be correlated. A huge knowledge gap was identified. The plausible mechanistic link for the association between periodontitis and neurodegenerative diseases is the interplay between periodontal inflammation and neuroinflammation. Three pathways are hypothesized in the literature, i.e., humoral, neuronal and cellular, with a clear role of periodontal pathogens, such as Porphyromonas gingivalis. Age, gender, race, smoking, alcohol intake, nutrition, physical activity, socioeconomic status, stress, medical comorbidities and genetics were identified as common risk factors for periodontitis and neurodegenerative diseases. Future research with main emphasis on the collaboration between neurologists and dentists is encouraged.
Full article
(This article belongs to the Special Issue Neuroinflammation in the Pathogenesis of Alzheimer's Disease and Related Dementias)
Open AccessArticle
Cross-Domain Text Mining of Pathophysiological Processes Associated with Diabetic Kidney Disease
by
Krutika Patidar, Jennifer H. Deng, Cassie S. Mitchell and Ashlee N. Ford Versypt
Int. J. Mol. Sci. 2024, 25(8), 4503; https://doi.org/10.3390/ijms25084503 - 19 Apr 2024
Abstract
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide. This study’s goal was to identify the signaling drivers and pathways that modulate glomerular endothelial dysfunction in DKD via artificial intelligence-enabled literature-based discovery. Cross-domain text mining of 33+ million PubMed
[...] Read more.
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide. This study’s goal was to identify the signaling drivers and pathways that modulate glomerular endothelial dysfunction in DKD via artificial intelligence-enabled literature-based discovery. Cross-domain text mining of 33+ million PubMed articles was performed with SemNet 2.0 to identify and rank multi-scalar and multi-factorial pathophysiological concepts related to DKD. A set of identified relevant genes and proteins that regulate different pathological events associated with DKD were analyzed and ranked using normalized mean HeteSim scores. High-ranking genes and proteins intersected three domains—DKD, the immune response, and glomerular endothelial cells. The top 10% of ranked concepts were mapped to the following biological functions: angiogenesis, apoptotic processes, cell adhesion, chemotaxis, growth factor signaling, vascular permeability, the nitric oxide response, oxidative stress, the cytokine response, macrophage signaling, NF B factor activity, the TLR pathway, glucose metabolism, the inflammatory response, the ERK/MAPK signaling response, the JAK/STAT pathway, the T-cell-mediated response, the WNT/ -catenin pathway, the renin–angiotensin system, and NADPH oxidase activity. High-ranking genes and proteins were used to generate a protein–protein interaction network. The study results prioritized interactions or molecules involved in dysregulated signaling in DKD, which can be further assessed through biochemical network models or experiments.
Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
►▼
Show Figures
Figure 1
Open AccessArticle
Integrative Bioinformatics–Gene Network Approach Reveals Linkage between Estrogenic Endocrine Disruptors and Vascular Remodeling in Peripheral Arterial Disease
by
Vincent Avecilla, Mayur Doke, Madhumita Das, Oscar Alcazar, Sandeep Appunni, Arthur Rech Tondin, Brandon Watts, Venkataraghavan Ramamoorthy, Muni Rubens and Jayanta Kumar Das
Int. J. Mol. Sci. 2024, 25(8), 4502; https://doi.org/10.3390/ijms25084502 - 19 Apr 2024
Abstract
Vascular diseases, including peripheral arterial disease (PAD), pulmonary arterial hypertension, and atherosclerosis, significantly impact global health due to their intricate relationship with vascular remodeling. This process, characterized by structural alterations in resistance vessels, is a hallmark of heightened vascular resistance seen in these
[...] Read more.
Vascular diseases, including peripheral arterial disease (PAD), pulmonary arterial hypertension, and atherosclerosis, significantly impact global health due to their intricate relationship with vascular remodeling. This process, characterized by structural alterations in resistance vessels, is a hallmark of heightened vascular resistance seen in these disorders. The influence of environmental estrogenic endocrine disruptors (EEDs) on the vasculature suggests a potential exacerbation of these alterations. Our study employs an integrative approach, combining data mining with bioinformatics, to unravel the interactions between EEDs and vascular remodeling genes in the context of PAD. We explore the molecular dynamics by which EED exposure may alter vascular function in PAD patients. The investigation highlights the profound effect of EEDs on pivotal genes such as ID3, LY6E, FOS, PTP4A1, NAMPT, GADD45A, PDGF-BB, and NFKB, all of which play significant roles in PAD pathophysiology. The insights gained from our study enhance the understanding of genomic alterations induced by EEDs in vascular remodeling processes. Such knowledge is invaluable for developing strategies to prevent and manage vascular diseases, potentially mitigating the impact of harmful environmental pollutants like EEDs on conditions such as PAD.
Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Molecular Mechanisms, Biomarkers, and Therapies)
►▼
Show Figures
Figure 1
Open AccessArticle
Human T-Cell Responses to Metallic Ion-Doped Bioactive Glasses
by
Hugo Abreu, Mari Lallukka, Marta Miola, Silvia Spriano, Enrica Vernè, Davide Raineri, Massimiliano Leigheb, Mario Ronga, Giuseppe Cappellano and Annalisa Chiocchetti
Int. J. Mol. Sci. 2024, 25(8), 4501; https://doi.org/10.3390/ijms25084501 - 19 Apr 2024
Abstract
Biomaterials are extensively used as replacements for damaged tissue with bioactive glasses standing out as bone substitutes for their intrinsic osteogenic properties. However, biomaterial implantation has the following risks: the development of implant-associated infections and adverse immune responses. Thus, incorporating metallic ions with
[...] Read more.
Biomaterials are extensively used as replacements for damaged tissue with bioactive glasses standing out as bone substitutes for their intrinsic osteogenic properties. However, biomaterial implantation has the following risks: the development of implant-associated infections and adverse immune responses. Thus, incorporating metallic ions with known antimicrobial properties can prevent infection, but should also modulate the immune response. Therefore, we selected silver, copper and tellurium as doping for bioactive glasses and evaluated the immunophenotype and cytokine profile of human T-cells cultured on top of these discs. Results showed that silver significantly decreased cell viability, copper increased the T helper (Th)-1 cell percentage while decreasing that of Th17, while tellurium did not affect either cell viability or immune response, as evaluated via multiparametric flow cytometry. Multiplex cytokines assay showed that IL-5 levels were decreased in the copper-doped discs, compared with its undoped control, while IL-10 tended to be lower in the doped glass, compared with the control (plastic) while undoped condition showed lower expression of IL-13 and increased MCP-1 and MIP-1β secretion. Overall, we hypothesized that the Th1/Th17 shift, and specific cytokine expression indicated that T-cells might cross-activate other cell types, potentially macrophages and eosinophils, in response to the scaffolds.
Full article
(This article belongs to the Section Materials Science)
►▼
Show Figures
Figure 1
Open AccessArticle
Revealing the Complete Bispecific Phosphatase Genes (DUSPs) across the Genome and Investigating the Expression Patterns of GH_A11G3500 Resistance against Verticillium Wilt
by
Yahui Deng, Xiaojuan Deng, Jieyin Zhao, Shuo Ning, Aixing Gu, Quanjia Chen and Yanying Qu
Int. J. Mol. Sci. 2024, 25(8), 4500; https://doi.org/10.3390/ijms25084500 - 19 Apr 2024
Abstract
DUSPs, a diverse group of protein phosphatases, play a pivotal role in orchestrating cellular growth and development through intricate signaling pathways. Notably, they actively participate in the MAPK pathway, which governs crucial aspects of plant physiology, including growth regulation, disease resistance, pest resistance,
[...] Read more.
DUSPs, a diverse group of protein phosphatases, play a pivotal role in orchestrating cellular growth and development through intricate signaling pathways. Notably, they actively participate in the MAPK pathway, which governs crucial aspects of plant physiology, including growth regulation, disease resistance, pest resistance, and stress response. DUSP is a key enzyme, and it is the enzyme that limits the rate of cell metabolism. At present, complete understanding of the DUSP gene family in cotton and its specific roles in resistance to Verticillium Wilt (VW) remains elusive. To address this knowledge gap, we conducted a comprehensive identification and analysis of four key cotton species: G. arboreum, G. barbadense, G. hirsutum, and G. raimondii. The results revealed the identification of a total of 120 DUSP genes in the four cotton varieties, which were categorized into six subgroups and randomly distributed at both ends of 26 chromosomes, predominantly localized within the nucleus. Our analysis demonstrated that closely related DUSP genes exhibited similarities in terms of the conserved motif composition and gene structure. A promoter analysis performed on the GhDUSP gene promoter revealed the presence of several cis-acting elements, which are associated with abiotic and biotic stress responses, as well as hormone signaling. A tissue expression pattern analysis demonstrated significant variations in GhDUSP gene expression under different stress conditions, with roots exhibiting the highest levels, followed by stems and leaves. In terms of tissue-specific detection, petals, leaves, stems, stamens, and receptacles exhibited higher expression levels of the GhDUSP gene. The gene expression analysis results for GhDUSPs under stress suggest that DUSP genes may have a crucial role in the cotton response to stress in cotton. Through Virus-Induced Gene Silencing (VIGS) experiments, the silencing of the target gene significantly reduced the resistance efficiency of disease-resistant varieties against Verticillium Wilt (VW). Consequently, we conclude that GH_A11G3500-mediated bispecific phosphorylated genes may serve as key regulators in the resistance of G. hirsutum to Verticillium Wilt (VW). This study presents a comprehensive structure designed to provide an in-depth understanding of the potential biological functions of cotton, providing a strong foundation for further research into molecular breeding and resistance to plant pathogens.
Full article
(This article belongs to the Special Issue Advances in Plant Breeding and Resistance)
Open AccessReview
On Connective Tissue Mast Cells as Protectors of Life, Reproduction, and Progeny
by
Klas Norrby
Int. J. Mol. Sci. 2024, 25(8), 4499; https://doi.org/10.3390/ijms25084499 - 19 Apr 2024
Abstract
The connective tissue mast cell (MC), a sentinel tissue-residing secretory immune cell, has been preserved in all vertebrate classes since approximately 500 million years. No physiological role of the MC has yet been established. Considering the power of natural selection of cells during
[...] Read more.
The connective tissue mast cell (MC), a sentinel tissue-residing secretory immune cell, has been preserved in all vertebrate classes since approximately 500 million years. No physiological role of the MC has yet been established. Considering the power of natural selection of cells during evolution, it is likely that the MCs exert essential yet unidentified life-promoting actions. All vertebrates feature a circulatory system, and the MCs interact readily with the vasculature. It is notable that embryonic MC progenitors are generated from endothelial cells. The MC hosts many surface receptors, enabling its activation via a vast variety of potentially harmful exogenous and endogenous molecules and via reproductive hormones in the female sex organs. Activated MCs release a unique composition of preformed and newly synthesized bioactive molecules, like heparin, histamine, serotonin, proteolytic enzymes, cytokines, chemokines, and growth factors. MCs play important roles in immune responses, tissue remodeling, cell proliferation, angiogenesis, inflammation, wound healing, tissue homeostasis, health, and reproduction. As recently suggested, MCs enable perpetuation of the vertebrates because of key effects—spanning generations—in ovulation and pregnancy, as in life-preserving activities in inflammation and wound healing from birth till reproductive age, thus creating a permanent life-sustaining loop. Here, we present recent advances that further indicate that the MC is a specific life-supporting and progeny-safeguarding cell.
Full article
(This article belongs to the Special Issue Advancements in Mast Cell Activation and Respiratory Conditions Updates)
Open AccessReview
Recent Advances in the Use of Stem Cells in Tissue Engineering and Adjunct Therapies for Tendon Reconstruction and Future Perspectives
by
Paweł Dec, Małgorzata Żyłka, Piotr Burszewski, Andrzej Modrzejewski and Andrzej Pawlik
Int. J. Mol. Sci. 2024, 25(8), 4498; https://doi.org/10.3390/ijms25084498 - 19 Apr 2024
Abstract
Due to their function, tendons are exposed to acute injuries. This type of damage to the musculoskeletal system represents a challenge for clinicians when natural regeneration and treatment methods do not produce the expected results. Currently, treatment is long and associated with long-term
[...] Read more.
Due to their function, tendons are exposed to acute injuries. This type of damage to the musculoskeletal system represents a challenge for clinicians when natural regeneration and treatment methods do not produce the expected results. Currently, treatment is long and associated with long-term complications. In this review, we discuss the use of stem cells in the treatment of tendons, including how to induce appropriate cell differentiation based on gene therapy, growth factors, tissue engineering, proteins involved in regenerative process, drugs and three-dimensional (3D) structures. A multidirectional approach as well as the incorporation of novel components of the therapy will improve the techniques used and benefit patients with tendon injuries in the future.
Full article
(This article belongs to the Special Issue Insights on the Role of Stem Cells in Tendon Tissue Engineering: From Basic Science to Translational Medicine)
Open AccessArticle
Genome-Wide Identification and Expression Analysis of Kiwifruit Leucine-Rich Repeat Receptor-like Proteins Reveal Their Roles in Biotic and Abiotic Stress Responses
by
Yingying Cao, Congxiao Zhang, Fang Liu, Dawei Li, Aidi Zhang, Li Li and Xiujun Zhang
Int. J. Mol. Sci. 2024, 25(8), 4497; https://doi.org/10.3390/ijms25084497 - 19 Apr 2024
Abstract
Leucine-rich repeat receptor-like proteins (LRR-RLPs), a major group of receptor-like proteins in plants, have diverse functions in plant physiology, including growth, development, signal transduction, and stress responses. Despite their importance, the specific roles of kiwifruit LRR-RLPs in response to biotic and
[...] Read more.
Leucine-rich repeat receptor-like proteins (LRR-RLPs), a major group of receptor-like proteins in plants, have diverse functions in plant physiology, including growth, development, signal transduction, and stress responses. Despite their importance, the specific roles of kiwifruit LRR-RLPs in response to biotic and abiotic stresses remain poorly understood. In this study, we performed family identification, characterization, transcriptome data analysis, and differential gene expression analysis of kiwifruit LRR-RLPs. We identified totals of 101, 164, and 105 LRR-RLPs in Actinidia Chinensis ‘Hongyang’, Actinidia eriantha ‘Huate’, and Actinidia chinensis ‘Red5’, respectively. Synteny analysis revealed that the expansion of kiwifruit LRR-RLPs was primarily attributed to segmental duplication events. Based on RNA-seq data from pathogen-infected kiwifruits, we identified specific LRR-RLP genes potentially involved in different stages of pathogen infection. Additionally, we observed the potential involvement of kiwifruit LRR-RLPs in abiotic stress responses, with upstream transcription factors possibly regulating their expression. Furthermore, protein interaction network analysis unveiled the participation of kiwifruit LRR-RLP in the regulatory network of abiotic stress responses. These findings highlight the crucial roles of LRR-RLPs in mediating both biotic and abiotic stress responses in kiwifruit, offering valuable insights for the breeding of stress-resistant kiwifruit varieties.
Full article
(This article belongs to the Special Issue Plant Physiology and Molecular Nutrition)
Open AccessArticle
Marrubiin Inhibits Peritoneal Inflammatory Response Induced by Carrageenan Application in C57 Mice
by
Niko S. Radulović, Miljana R. Đorđević Zlatković, Nikola M. Stojanović, Milan S. Nešić, Dragan B. Zlatković, Milena S. Potić Floranović, Dragana S. Tričković Vukić and Pavle J. Randjelovic
Int. J. Mol. Sci. 2024, 25(8), 4496; https://doi.org/10.3390/ijms25084496 - 19 Apr 2024
Abstract
Marrubiin is a diterpene with a long history of a wide range of biological activities. In this study, the anti-inflammatory effects of marrubiin were investigated using several in vitro and in vivo assays. Marrubiin inhibited carrageenan-induced peritoneal inflammation by preventing inflammatory cell infiltration
[...] Read more.
Marrubiin is a diterpene with a long history of a wide range of biological activities. In this study, the anti-inflammatory effects of marrubiin were investigated using several in vitro and in vivo assays. Marrubiin inhibited carrageenan-induced peritoneal inflammation by preventing inflammatory cell infiltration and peritoneal mast cell degranulation. The anti-inflammatory activity was further demonstrated by monitoring a set of biochemical parameters, showing that the peritoneal fluid of animals treated with marrubiin had lower levels of proteins and lower myeloperoxidase activity compared with the fluid of animals that were not treated. Marrubiin exerted the most pronounced cytotoxic activity towards peripheral mononuclear cells, being the main contributors to peritoneal inflammation. Additionally, a moderate lipoxygenase inhibition activity of marrubiin was observed.
Full article
(This article belongs to the Section Molecular Immunology)
Open AccessArticle
NF-κB in the Radiation Response of A549 Non-Small Cell Lung Cancer Cells to X-rays and Carbon Ions under Hypoxia
by
Hasan Nisar, Paulina Mercedes Sanchidrián González, Frederik M. Labonté, Claudia Schmitz, Marie Denise Roggan, Jessica Kronenberg, Bikash Konda, François Chevalier and Christine E. Hellweg
Int. J. Mol. Sci. 2024, 25(8), 4495; https://doi.org/10.3390/ijms25084495 - 19 Apr 2024
Abstract
Cellular hypoxia, detectable in up to 80% of non-small cell lung carcinoma (NSCLC) tumors, is a known cause of radioresistance. High linear energy transfer (LET) particle radiation might be effective in the treatment of hypoxic solid tumors, including NSCLC. Cellular hypoxia can activate
[...] Read more.
Cellular hypoxia, detectable in up to 80% of non-small cell lung carcinoma (NSCLC) tumors, is a known cause of radioresistance. High linear energy transfer (LET) particle radiation might be effective in the treatment of hypoxic solid tumors, including NSCLC. Cellular hypoxia can activate nuclear factor κB (NF-κB), which can modulate radioresistance by influencing cancer cell survival. The effect of high-LET radiation on NF-κB activation in hypoxic NSCLC cells is unclear. Therefore, we compared the effect of low (X-rays)- and high (12C)-LET radiation on NF-κB responsive genes’ upregulation, as well as its target cytokines’ synthesis in normoxic and hypoxic A549 NSCLC cells. The cells were incubated under normoxia (20% O2) or hypoxia (1% O2) for 48 h, followed by irradiation with 8 Gy X-rays or 12C ions, maintaining the oxygen conditions until fixation or lysis. Regulation of NF-κB responsive genes was evaluated by mRNA sequencing. Secretion of NF-κB target cytokines, IL-6 and IL-8, was quantified by ELISA. A greater fold change increase in expression of NF-κB target genes in A549 cells following exposure to 12C ions compared to X-rays was observed, regardless of oxygenation status. These genes regulate cell migration, cell cycle, and cell survival. A greater number of NF-κB target genes was activated under hypoxia, regardless of irradiation status. These genes regulate cell migration, survival, proliferation, and inflammation. X-ray exposure under hypoxia additionally upregulated NF-κB target genes modulating immunosurveillance and epithelial-mesenchymal transition (EMT). Increased IL-6 and IL-8 secretion under hypoxia confirmed NF-κB-mediated expression of pro-inflammatory genes. Therefore, radiotherapy, particularly with X-rays, may increase tumor invasiveness in surviving hypoxic A549 cells.
Full article
(This article belongs to the Section Molecular Oncology)
Open AccessArticle
Molecular Epidemiology of Carbapenem-Resistant Klebsiella aerogenes in Japan
by
Kentarou Takei, Miho Ogawa, Ryuji Sakata and Hajime Kanamori
Int. J. Mol. Sci. 2024, 25(8), 4494; https://doi.org/10.3390/ijms25084494 - 19 Apr 2024
Abstract
Information regarding Klebsiella aerogenes haboring carbapenemase in Japan is limited. A comprehensive nationwide survey was conducted from September 2014 to December 2022, and 67 non-duplicate strains of carbapenem-resistant K. aerogenes were isolated from 57 healthcare facilities in Japan. Through genetic testing and whole-genome
[...] Read more.
Information regarding Klebsiella aerogenes haboring carbapenemase in Japan is limited. A comprehensive nationwide survey was conducted from September 2014 to December 2022, and 67 non-duplicate strains of carbapenem-resistant K. aerogenes were isolated from 57 healthcare facilities in Japan. Through genetic testing and whole-genome sequencing, six strains were found to possess carbapenemases, including imipenemase (IMP)-1, IMP-6, New Delhi metallo-β-lactamase (NDM)-1, and NDM-5. The strain harboring blaNDM-5 was the novel strain ST709, which belongs to the clonal complex of the predominant ST4 in China. The novel integron containing blaIMP-1 featured the oxacillinase-101 gene, which is a previously unreported structure, with an IncN4 plasmid type. However, integrons found in the strains possessing blaIMP-6, which were the most commonly identified, matched those reported domestically in Klebsiella pneumoniae, suggesting the prevalence of identical integrons. Transposons containing blaNDM are similar or identical to the transposon structure of K. aerogenes harboring blaNDM-5 previously reported in Japan, suggesting that the same type of transposon could have been transmitted to K. aerogenes in Japan. This investigation analyzed mobile genetic elements, such as integrons and transposons, to understand the spread of carbapenemases, highlighting the growing challenge of carbapenem-resistant Enterobacterales in Japan and underscoring the critical need for ongoing surveillance to control these pathogens.
Full article
(This article belongs to the Special Issue Applications of Nanomaterials in the Antimicrobial Sector)
Open AccessArticle
Missing WD40 Repeats in ATG16L1 Delays Canonical Autophagy and Inhibits Noncanonical Autophagy
by
Jiuge Tang, Dongmei Fang, Jialing Zhong and Min Li
Int. J. Mol. Sci. 2024, 25(8), 4493; https://doi.org/10.3390/ijms25084493 - 19 Apr 2024
Abstract
Canonical autophagy is an evolutionarily conserved process that forms double-membrane structures and mediates the degradation of long-lived proteins (LLPs). Noncanonical autophagy (NCA) is an important alternative pathway involving the formation of microtubule-associated protein 1 light chain 3 (LC3)-positive structures that are independent of
[...] Read more.
Canonical autophagy is an evolutionarily conserved process that forms double-membrane structures and mediates the degradation of long-lived proteins (LLPs). Noncanonical autophagy (NCA) is an important alternative pathway involving the formation of microtubule-associated protein 1 light chain 3 (LC3)-positive structures that are independent of partial core autophagy proteins. NCA has been defined by the conjugation of ATG8s to single membranes (CASM). During canonical autophagy and NCA/CASM, LC3 undergoes a lipidation modification, and ATG16L1 is a crucial protein in this process. Previous studies have reported that the WDR domain of ATG16L1 is not necessary for canonical autophagy. However, our study found that WDR domain deficiency significantly impaired LLP degradation in basal conditions and slowed down LC3-II accumulation in canonical autophagy. We further demonstrated that the observed effect was due to a reduced interaction between ATG16L1 and FIP200/WIPI2, without affecting lysosome function or fusion. Furthermore, we also found that the WDR domain of ATG16L1 is crucial for chemical-induced NCA/CASM. The results showed that removing the WDR domain or introducing the K490A mutation in ATG16L1 significantly inhibited the NCA/CASM, which interrupted the V-ATPase-ATG16L1 axis. In conclusion, this study highlights the significance of the WDR domain of ATG16L1 for both canonical autophagy and NCA functions, improving our understanding of its role in autophagy.
Full article
(This article belongs to the Special Issue Molecular Research on Autophagy)
Open AccessReview
The Role of Extracellular Vesicles in Allergic Sensitization: A Systematic Review
by
Davis Tucis, Georgina Hopkins, William Browne, Victoria James, David Onion and Lucy C. Fairclough
Int. J. Mol. Sci. 2024, 25(8), 4492; https://doi.org/10.3390/ijms25084492 - 19 Apr 2024
Abstract
Allergies affect approximately 10–30% of people worldwide, with an increasing number of cases each year; however, the underlying mechanisms are still poorly understood. In recent years, extracellular vesicles (EVs) have been suggested to play a role in allergic sensitization and skew to a
[...] Read more.
Allergies affect approximately 10–30% of people worldwide, with an increasing number of cases each year; however, the underlying mechanisms are still poorly understood. In recent years, extracellular vesicles (EVs) have been suggested to play a role in allergic sensitization and skew to a T helper type 2 (Th2) response. The aim of this review is to highlight the existing evidence of EV involvement in allergies. A total of 22 studies were reviewed; 12 studies showed EVs can influence a Th2 response, while 10 studies found EVs promoted a Th1 or Treg response. EVs can drive allergic sensitization through up-regulation of pro-Th2 cytokines, such as IL-4 and IL-13. In addition, EVs from MRSA can induce IgE hypersensitivity in mice towards MRSA. On the other hand, EVs can induce tolerance in the immune system; for example, pre-exposing OVA-loaded EVs prevented OVA sensitization in mice. The current literature thus suggests that EVs play an essential role in allergy. Further research utilizing human in vitro models and clinical studies is needed to give a reliable account of the role of EVs in allergy.
Full article
(This article belongs to the Special Issue The Molecular Basis of Extracellular Vesicles in Health and Diseases)
Open AccessReview
Mitochondrial Kinase Signaling for Cardioprotection
by
Kerstin Boengler, Chantal Eickelmann and Petra Kleinbongard
Int. J. Mol. Sci. 2024, 25(8), 4491; https://doi.org/10.3390/ijms25084491 - 19 Apr 2024
Abstract
Myocardial ischemia/reperfusion injury is reduced by cardioprotective adaptations such as local or remote ischemic conditioning. The cardioprotective stimuli activate signaling cascades, which converge on mitochondria and maintain the function of the organelles, which is critical for cell survival. The signaling cascades include not
[...] Read more.
Myocardial ischemia/reperfusion injury is reduced by cardioprotective adaptations such as local or remote ischemic conditioning. The cardioprotective stimuli activate signaling cascades, which converge on mitochondria and maintain the function of the organelles, which is critical for cell survival. The signaling cascades include not only extracellular molecules that activate sarcolemmal receptor-dependent or -independent protein kinases that signal at the plasma membrane or in the cytosol, but also involve kinases, which are located to or within mitochondria, phosphorylate mitochondrial target proteins, and thereby modify, e.g., respiration, the generation of reactive oxygen species, calcium handling, mitochondrial dynamics, mitophagy, or apoptosis. In the present review, we give a personal and opinionated overview of selected protein kinases, localized to/within myocardial mitochondria, and summarize the available data on their role in myocardial ischemia/reperfusion injury and protection from it. We highlight the regulation of mitochondrial function by these mitochondrial protein kinases.
Full article
(This article belongs to the Topic Molecular and Cellular Mechanisms of Diseases: Heart Disease)
Open AccessReview
Analysis and Characterization of the Extracellular Vesicles Released in Non-Cancer Diseases Using Matrix-Assisted Laser Desorption Ionization/Mass Spectrometry
by
Antonella Maria Aresta, Nicoletta De Vietro and Carlo Zambonin
Int. J. Mol. Sci. 2024, 25(8), 4490; https://doi.org/10.3390/ijms25084490 - 19 Apr 2024
Abstract
The extracellular vesicles (EVs) released by cells play a crucial role in intercellular communications and interactions. The direct shedding of EVs from the plasma membrane represents a fundamental pathway for the transfer of properties and information between cells. These vesicles are classified based
[...] Read more.
The extracellular vesicles (EVs) released by cells play a crucial role in intercellular communications and interactions. The direct shedding of EVs from the plasma membrane represents a fundamental pathway for the transfer of properties and information between cells. These vesicles are classified based on their origin, biogenesis, size, content, surface markers, and functional features, encompassing a variety of bioactive molecules that reflect the physiological state and cell type of origin. Such molecules include lipids, nucleic acids, and proteins. Research efforts aimed at comprehending EVs, including the development of strategies for their isolation, purification, and characterization, have led to the discovery of new biomarkers. These biomarkers are proving invaluable for diagnosing diseases, monitoring disease progression, understanding treatment responses, especially in oncology, and addressing metabolic, neurological, infectious disorders, as well as advancing vaccine development. Matrix-Assisted Laser Desorption Ionization (MALDI)/Mass Spectrometry (MS) stands out as a leading tool for the analysis and characterization of EVs and their cargo. This technique offers inherent advantages such as a high throughput, minimal sample consumption, rapid and cost-effective analysis, and user-friendly operation. This review is mainly focused on the primary applications of MALDI–time-of-flight (TOF)/MS in the analysis and characterization of extracellular vesicles associated with non-cancerous diseases and pathogens that infect humans, animals, and plants.
Full article
(This article belongs to the Special Issue Exosomes and Extracellular Vesicles in Health and Diseases 2.0)
Open AccessArticle
Dysregulated VEGF/VEGFR-2 Signaling and Plexogenic Lesions in the Embryonic Lungs of Chickens Predisposed to Pulmonary Arterial Hypertension
by
Lujie Ye, Rui Liu, Qinghao Li, Chunzhen Zhou and Xun Tan
Int. J. Mol. Sci. 2024, 25(8), 4489; https://doi.org/10.3390/ijms25084489 - 19 Apr 2024
Abstract
Plexiform lesions are a hallmark of pulmonary arterial hypertension (PAH) in humans and are proposed to stem from dysfunctional angioblasts. Broiler chickens (Gallus gallus) are highly susceptible to PAH, with plexiform-like lesions observed in newly hatched individuals. Here, we reported the
[...] Read more.
Plexiform lesions are a hallmark of pulmonary arterial hypertension (PAH) in humans and are proposed to stem from dysfunctional angioblasts. Broiler chickens (Gallus gallus) are highly susceptible to PAH, with plexiform-like lesions observed in newly hatched individuals. Here, we reported the emergence of plexiform-like lesions in the embryonic lungs of broiler chickens. Lung samples were collected from broiler chickens at embryonic day 20 (E20), hatch, and one-day-old, with PAH-resistant layer chickens as controls. Plexiform lesions consisting of CD133+/vascular endothelial growth factor receptor type-2 (VEGFR-2)+ angioblasts were exclusively observed in broiler embryos and sporadically in layer embryos. Distinct gene profiles of angiogenic factors were observed between the two strains, with impaired VEGF-A/VEGFR-2 signaling correlating with lesion development and reduced arteriogenesis. Pharmaceutical inhibition of VEGFR-2 resulted in enhanced lesion development in layer embryos. Moreover, broiler embryonic lungs displayed increased activation of HIF-1α and nuclear factor erythroid 2-related factor 2 (Nrf2), indicating a hypoxic state. Remarkably, we found a negative correlation between lung Nrf2 activation and VEGF-A and VEGFR-2 expression. In vitro studies indicated that Nrf2 overactivation restricted VEGF signaling in endothelial progenitor cells. The findings from broiler embryos suggest an association between plexiform lesion development and impaired VEGF system due to aberrant activation of Nrf2.
Full article
(This article belongs to the Special Issue Advance in Molecular Pathology of Pulmonary Hypertension)
►▼
Show Figures
Figure 1
Journal Menu
► ▼ Journal Menu-
- IJMS Home
- Aims & Scope
- Editorial Board
- Reviewer Board
- Topical Advisory Panel
- Instructions for Authors
- Special Issues
- Topics
- Sections & Collections
- Article Processing Charge
- Indexing & Archiving
- Most Cited & Viewed
- Journal Statistics
- Journal History
- Journal Awards
- Society Collaborations
- Conferences
- Editorial Office
Journal Browser
► ▼ Journal Browser-
arrow_forward_ios
Forthcoming issue
arrow_forward_ios Current issue - Vol. 25 (2024)
- Vol. 24 (2023)
- Vol. 23 (2022)
- Vol. 22 (2021)
- Vol. 21 (2020)
- Vol. 20 (2019)
- Vol. 19 (2018)
- Vol. 18 (2017)
- Vol. 17 (2016)
- Vol. 16 (2015)
- Vol. 15 (2014)
- Vol. 14 (2013)
- Vol. 13 (2012)
- Vol. 12 (2011)
- Vol. 11 (2010)
- Vol. 10 (2009)
- Vol. 9 (2008)
- Vol. 8 (2007)
- Vol. 7 (2006)
- Vol. 6 (2005)
- Vol. 5 (2004)
- Vol. 4 (2003)
- Vol. 3 (2002)
- Vol. 2 (2001)
- Vol. 1 (2000)
Highly Accessed Articles
Latest Books
E-Mail Alert
News
Topics
Topic in
Biomolecules, Cells, Genes, IJMS, ncRNA
MicroRNA: Mechanisms of Action, Physio-Pathological Implications, and Disease Biomarkers, 2nd Volume
Topic Editors: Y-h. Taguchi, Hsiuying WangDeadline: 20 April 2024
Topic in
Biomedicines, Cells, IJMS, Life, Oxygen
Oxidative Stress and Inflammation, 2nd Volume
Topic Editors: Mohamad Allaw, Ines Castangia, Maria Letizia Manca, Matteo Perra, Amparo NacherDeadline: 31 May 2024
Topic in
BioChem, Biomedicines, Biomolecules, IJMS, Metabolites, Molecules
Natural Products in Prevention and Therapy of Metabolic Syndrome
Topic Editors: Jianbo Wan, Ligen LinDeadline: 30 June 2024
Topic in
Cells, Diseases, Healthcare, IJMS, Vaccines
Inflammation: The Cause of all Diseases 2.0
Topic Editors: Vasso Apostolopoulos, Jack Feehan, Vivek P. ChavdaDeadline: 31 July 2024
Conferences
Special Issues
Special Issue in
IJMS
High-Density Lipoproteins in Health and Disease
Guest Editor: Ilaria ZanottiDeadline: 20 April 2024
Special Issue in
IJMS
Monoclonal Antibodies and Their Functional Fragments in Research, Diagnosis and Therapy 3.0
Guest Editors: Menotti Ruvo, Annamaria SandomenicoDeadline: 30 April 2024
Special Issue in
IJMS
Pharmacogenetics and Personalized Medicine 3.0
Guest Editors: José A. Riancho, Gloria RavegniniDeadline: 20 May 2024
Special Issue in
IJMS
Molecular Mechanisms of Angiogenesis and Cancer
Guest Editor: Vijay AvinDeadline: 30 May 2024
Topical Collections
Topical Collection in
IJMS
Feature Papers in Bioactives and Nutraceuticals
Collection Editor: Maurizio Battino
Topical Collection in
IJMS
State-of-the-Art Molecular Microbiology in Poland
Collection Editors: Alicja Wegrzyn, Satish Raina
Topical Collection in
IJMS
Computational, Structural and Spectroscopic Studies of Enzyme Mechanisms, Inhibition and Dynamics
Collection Editor: Christo Christov