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 15.9 days after submission; acceptance to publication is undertaken in 2.9 days (median values for papers published in this journal in the second half of 2022).
- 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:
6.208 (2021);
5-Year Impact Factor:
6.628 (2021)
Latest Articles
Preleukemic Fusion Genes Induced via Ionizing Radiation
Int. J. Mol. Sci. 2023, 24(7), 6580; https://doi.org/10.3390/ijms24076580 (registering DOI) - 01 Apr 2023
Abstract
Although the prevalence of leukemia is increasing, the agents responsible for this increase are not definitely known. While ionizing radiation (IR) was classified as a group one carcinogen by the IARC, the IR-induced cancers, including leukemia, are indistinguishable from those that are caused
[...] Read more.
Although the prevalence of leukemia is increasing, the agents responsible for this increase are not definitely known. While ionizing radiation (IR) was classified as a group one carcinogen by the IARC, the IR-induced cancers, including leukemia, are indistinguishable from those that are caused by other factors, so the risk estimation relies on epidemiological data. Several epidemiological studies on atomic bomb survivors and persons undergoing IR exposure during medical investigations or radiotherapy showed an association between radiation and leukemia. IR is also known to induce chromosomal translocations. Specific chromosomal translocations resulting in preleukemic fusion genes (PFGs) are generally accepted to be the first hit in the onset of many leukemias. Several studies indicated that incidence of PFGs in healthy newborns is up to 100-times higher than childhood leukemia with the same chromosomal aberrations. Because of this fact, it has been suggested that PFGs are not able to induce leukemia alone, but secondary mutations are necessary. PFGs also have to occur in specific cell populations of hematopoetic stem cells with higher leukemogenic potential. In this review, we describe the connection between IR, PFGs, and cancer, focusing on recurrent PFGs where an association with IR has been established.
Full article
(This article belongs to the Collection Feature Papers in Molecular Oncology)
►
Show Figures
Open AccessReview
Diet as a Source of Acrolein: Molecular Basis of Aldehyde Biological Activity in Diabetes and Digestive System Diseases
by
and
Int. J. Mol. Sci. 2023, 24(7), 6579; https://doi.org/10.3390/ijms24076579 (registering DOI) - 31 Mar 2023
Abstract
Acrolein, a highly reactive α,β-unsaturated aldehyde, is a compound involved in the pathogenesis of many diseases, including neurodegenerative diseases, cardiovascular and respiratory diseases, diabetes mellitus, and the development of cancers of various origins. In addition to environmental pollution (e.g., from car exhaust fumes)
[...] Read more.
Acrolein, a highly reactive α,β-unsaturated aldehyde, is a compound involved in the pathogenesis of many diseases, including neurodegenerative diseases, cardiovascular and respiratory diseases, diabetes mellitus, and the development of cancers of various origins. In addition to environmental pollution (e.g., from car exhaust fumes) and tobacco smoke, a serious source of acrolein is our daily diet and improper thermal processing of animal and vegetable fats, carbohydrates, and amino acids. Dietary intake is one of the main routes of human exposure to acrolein, which is a major public health concern. This review focuses on the molecular mechanisms of acrolein activity in the context of its involvement in the pathogenesis of diseases related to the digestive system, including diabetes, alcoholic liver disease, and intestinal cancer.
Full article
(This article belongs to the Section Molecular Biology)
Open AccessReview
Advances in the Pathogenesis and Treatment of Systemic Lupus Erythematosus
by
, , , , , and
Int. J. Mol. Sci. 2023, 24(7), 6578; https://doi.org/10.3390/ijms24076578 (registering DOI) - 31 Mar 2023
Abstract
Systemic lupus erythematosus (SLE) is a genetically predisposed, female-predominant disease, characterized by multiple organ damage, that in its most severe forms can be life-threatening. The pathogenesis of SLE is complex and involves cells of both innate and adaptive immunity. The distinguishing feature of
[...] Read more.
Systemic lupus erythematosus (SLE) is a genetically predisposed, female-predominant disease, characterized by multiple organ damage, that in its most severe forms can be life-threatening. The pathogenesis of SLE is complex and involves cells of both innate and adaptive immunity. The distinguishing feature of SLE is the production of autoantibodies, with the formation of immune complexes that precipitate at the vascular level, causing organ damage. Although progress in understanding the pathogenesis of SLE has been slower than in other rheumatic diseases, new knowledge has recently led to the development of effective targeted therapies, that hold out hope for personalized therapy. However, the new drugs available to date are still an adjunct to conventional therapy, which is known to be toxic in the short and long term. The purpose of this review is to summarize recent advances in understanding the pathogenesis of the disease and discuss the results obtained from the use of new targeted drugs, with a look at future therapies that may be used in the absence of the current standard of care or may even cure this serious systemic autoimmune disease.
Full article
(This article belongs to the Special Issue Recent Advances in Immunotheragnostics: From Molecular Basis to Targeted Pharmaceutical Design 2.0)
Open AccessArticle
Signatures of Co-Deregulated Genes and Their Transcriptional Regulators in Kidney Cancers
by
, , , , and
Int. J. Mol. Sci. 2023, 24(7), 6577; https://doi.org/10.3390/ijms24076577 (registering DOI) - 31 Mar 2023
Abstract
There are several studies on the deregulated gene expression profiles in kidney cancer, with varying results depending on the tumor histology and other parameters. None of these, however, have identified the networks that the co-deregulated genes (co-DEGs), across different studies, create. Here, we
[...] Read more.
There are several studies on the deregulated gene expression profiles in kidney cancer, with varying results depending on the tumor histology and other parameters. None of these, however, have identified the networks that the co-deregulated genes (co-DEGs), across different studies, create. Here, we reanalyzed 10 Gene Expression Omnibus (GEO) studies to detect and annotate co-deregulated signatures across different subtypes of kidney cancer or in single-gene perturbation experiments in kidney cancer cells and/or tissue. Using a systems biology approach, we aimed to decipher the networks they form along with their upstream regulators. Differential expression and upstream regulators, including transcription factors [MYC proto-oncogene (MYC), CCAAT enhancer binding protein delta (CEBPD), RELA proto-oncogene, NF-kB subunit (RELA), zinc finger MIZ-type containing 1 (ZMIZ1), negative elongation factor complex member E (NELFE) and Kruppel-like factor 4 (KLF4)] and protein kinases [Casein kinase 2 alpha 1 (CSNK2A1), mitogen-activated protein kinases 1 (MAPK1) and 14 (MAPK14), Sirtuin 1 (SIRT1), Cyclin dependent kinases 1 (CDK1) and 4 (CDK4), Homeodomain interacting protein kinase 2 (HIPK2) and Extracellular signal-regulated kinases 1 and 2 (ERK1/2)], were computed using the Characteristic Direction, as well as GEO2Enrichr and X2K, respectively, and further subjected to GO and KEGG pathways enrichment analyses. Furthermore, using CMap, DrugMatrix and the LINCS L1000 chemical perturbation databases, we highlight putative repurposing drugs, including Etoposide, Haloperidol, BW-B70C, Triamterene, Chlorphenesin, BRD-K79459005 and β-Estradiol 3-benzoate, among others, that may reverse the expression of the identified co-DEGs in kidney cancers. Of these, the cytotoxic effects of Etoposide, Catecholamine, Cyclosporin A, BW-B70C and Lasalocid sodium were validated in vitro. Overall, we identified critical co-DEGs across different subtypes in kidney cancer, and our results provide an innovative framework for their potential use in the future.
Full article
(This article belongs to the Special Issue Data Science in Cancer Genomics and Precision Medicine)
Open AccessArticle
Clinical Consequences and Functional Impact of the Rare S737F CFTR Variant and Its Responsiveness to CFTR Modulators
by
, , , , , , , , , , and
Int. J. Mol. Sci. 2023, 24(7), 6576; https://doi.org/10.3390/ijms24076576 (registering DOI) - 31 Mar 2023
Abstract
S737F is a cystic fibrosis (CF) transmembrane conductance regulator (CFTR) missense variant. The aim of our study was to describe the clinical features of a cohort of individuals carrying this variant. In parallel, by exploiting ex vivo functional and molecular analyses on nasal
[...] Read more.
S737F is a cystic fibrosis (CF) transmembrane conductance regulator (CFTR) missense variant. The aim of our study was to describe the clinical features of a cohort of individuals carrying this variant. In parallel, by exploiting ex vivo functional and molecular analyses on nasal epithelia derived from a subset of S737F carriers, we evaluated its functional impact on CFTR protein, as well as its responsiveness to CFTR modulators. We retrospectively collected clinical data of all individuals bearing at least one S737F CFTR variant and followed at the CF Centre of Tuscany region (Italy). Nasal brushing was performed in cooperating individuals. At study end clinical data were available for 10 subjects (mean age: 14 years; range 1–44 years; three adult individuals). Five asymptomatic subjects had CF, and two were CRMS/CFSPID, and three had an inconclusive diagnosis. Ex vivo analysis on nasal epithelia demonstrated different levels of CF activity. In particular, epithelia derived from asymptomatic CF subjects and from one of the subjects with inconclusive diagnosis showed reduced CFTR activity that could be rescued by treatment with CFTR modulators. On the contrary, in the epithelia derived from the other two individuals with an inconclusive diagnosis, the CFTR-mediated current was similar to that observed in epithelia derived from healthy donors. In vitro functional and biochemical analysis on S737F-CFTR expressed in immortalized bronchial cells highlighted a modest impairment of the channel activity, which was improved by treatment with ivacaftor alone or in combination with tezacaftor/elexacaftor. Our study provide evidence towards the evaluation of CFTR function on ex vivo nasal epithelial cell models as a new assay to help clinicians to classify individuals, in presence of discordance between clinical picture, sweat test, and genetic profile.
Full article
(This article belongs to the Special Issue Molecular Pathology and Therapy on Cystic Fibrosis and CFTR-Related Diseases)
Open AccessArticle
Cadmium Exposure Is Associated with Behavioral Deficits and Neuroimmune Dysfunction in BTBR T+ Itpr3tf/J Mice
by
, , , , , , , , , , and
Int. J. Mol. Sci. 2023, 24(7), 6575; https://doi.org/10.3390/ijms24076575 (registering DOI) - 31 Mar 2023
Abstract
Autism spectrum disorders (ASD) are neurobehavioral disabilities characterized by impaired social interactions, poor communication skills, and restrictive/repetitive behaviors. Cadmium is a common heavy metal implicated in ASD. In this study, we investigated the effects of Cd exposure on BTBR T+ Itpr3tf/J (BTBR) mice,
[...] Read more.
Autism spectrum disorders (ASD) are neurobehavioral disabilities characterized by impaired social interactions, poor communication skills, and restrictive/repetitive behaviors. Cadmium is a common heavy metal implicated in ASD. In this study, we investigated the effects of Cd exposure on BTBR T+ Itpr3tf/J (BTBR) mice, an ASD model. We looked for changes in repetitive behaviors and sociability through experiments. We also explored the molecular mechanisms underlying the effects of Cd exposure, focusing on proinflammatory cytokines and pathways. Flow cytometry measured IL-17A-, IL-17F-, IL-21-, TNF-α-, STAT3-, and RORγt-expressing CD4+ T cells from the spleens of experimental mice. We then used RT-PCR to analyze IL-17A, IL-17F, IL-21, TNF-α, STAT3, and RORγ mRNA expression in the brain. The results of behavioral experiments showed that Cd exposure significantly increased self-grooming and marble-burying in BTBR mice while decreasing social interactions. Cd exposure also significantly increased the number of CD4+IL-17A+, CD4+IL-17F+, CD4+IL-21+, CD4+TNF-α+, CD4+STAT3+, and CD4+RORγt+ cells, while upregulating the mRNA expression of the six molecules in the brain. Overall, our results suggest that oral exposure to Cd aggravates behavioral and immune abnormalities in an ASD animal model. These findings have important implications for ASD etiology and provide further evidence of heavy metals contributing to neurodevelopmental disorders through proinflammatory effects.
Full article
(This article belongs to the Special Issue Advances in Neurogenetics and Neuroimmunology)
Open AccessArticle
Abundance of Transgene Transcript Variants Associated with Somatically Active Transgenic Helitrons from Multiple T-DNA Integration Sites in Maize
Int. J. Mol. Sci. 2023, 24(7), 6574; https://doi.org/10.3390/ijms24076574 (registering DOI) - 31 Mar 2023
Abstract
Helitrons, a novel type of mysterious DNA transposons discovered computationally prior to bench work confirmation, are components ubiquitous in most sequenced genomes of various eukaryotes, including plants, animals, and fungi. There is a paucity of empirical evidence to elucidate the mechanism of
[...] Read more.
Helitrons, a novel type of mysterious DNA transposons discovered computationally prior to bench work confirmation, are components ubiquitous in most sequenced genomes of various eukaryotes, including plants, animals, and fungi. There is a paucity of empirical evidence to elucidate the mechanism of Helitrons transposition in plants. Here, by constructing several artificial defective Helitron (dHel) reporter systems, we aim to identify the autonomous Helitrons (aHel) in maize genetically and to demonstrate the transposition and repair mechanisms of Helitrons upon the dHel-GFP excision in maize. When crossing with various inbred lines, several transgenic lines produced progeny of segregated, purple-blotched kernels, resulting from a leaky expression of the C1 gene driven by the dHel-interrupted promoter. Transcription analysis indicated that the insertion of different dHels into the C1 promoter or exon would lead to multiple distinct mRNA transcripts corresponding to transgenes in the host genome. Simple excision products and circular intermediates of dHel-GFP transposition have been detected from the leaf tissue of the seedlings in F1 hybrids of transgenic lines with corresponding c1 tester, although they failed to be detected in all primary transgenic lines. These results revealed the transposition and repair mechanism of Helitrons in maize. It is strongly suggested that this reporter system can detect the genetic activity of autonomic Helitron at the molecular level. Sequence features of dHel itself, together with the flanking regions, impact the excision activity of dHel and the regulation of the dHel on the transcription level of the host gene.
Full article
(This article belongs to the Special Issue Molecular Genetics and Plant Breeding 3.0)
Open AccessReview
A Systematic Review of Deep Learning Methodologies Used in the Drug Discovery Process with Emphasis on In Vivo Validation
by
, , , and
Int. J. Mol. Sci. 2023, 24(7), 6573; https://doi.org/10.3390/ijms24076573 (registering DOI) - 31 Mar 2023
Abstract
The discovery and development of new drugs are extremely long and costly processes. Recent progress in artificial intelligence has made a positive impact on the drug development pipeline. Numerous challenges have been addressed with the growing exploitation of drug-related data and the advancement
[...] Read more.
The discovery and development of new drugs are extremely long and costly processes. Recent progress in artificial intelligence has made a positive impact on the drug development pipeline. Numerous challenges have been addressed with the growing exploitation of drug-related data and the advancement of deep learning technology. Several model frameworks have been proposed to enhance the performance of deep learning algorithms in molecular design. However, only a few have had an immediate impact on drug development since computational results may not be confirmed experimentally. This systematic review aims to summarize the different deep learning architectures used in the drug discovery process and are validated with further in vivo experiments. For each presented study, the proposed molecule or peptide that has been generated or identified by the deep learning model has been biologically evaluated in animal models. These state-of-the-art studies highlight that even if artificial intelligence in drug discovery is still in its infancy, it has great potential to accelerate the drug discovery cycle, reduce the required costs, and contribute to the integration of the 3R (Replacement, Reduction, Refinement) principles. Out of all the reviewed scientific articles, seven algorithms were identified: recurrent neural networks, specifically, long short-term memory (LSTM-RNNs), Autoencoders (AEs) and their Wasserstein Autoencoders (WAEs) and Variational Autoencoders (VAEs) variants; Convolutional Neural Networks (CNNs); Direct Message Passing Neural Networks (D-MPNNs); and Multitask Deep Neural Networks (MTDNNs). LSTM-RNNs were the most used architectures with molecules or peptide sequences as inputs.
Full article
(This article belongs to the Special Issue Latest Review Papers in Molecular Pharmacology 2023)
Open AccessArticle
Polymorphism of Butyl Ester of Oleanolic Acid—The Dominance of Dispersive Interactions over Electrostatic
by
, , , , and
Int. J. Mol. Sci. 2023, 24(7), 6572; https://doi.org/10.3390/ijms24076572 (registering DOI) - 31 Mar 2023
Abstract
Oleanolic (OA) and glycyrrhetinic acids (GE), as well as their derivatives, show a variety of pharmacological properties. Their crystal structures provide valuable information related to the assembly modes of these biologically active compounds. In the known-to-date crystals of OA esters, their 11-oxo derivatives,
[...] Read more.
Oleanolic (OA) and glycyrrhetinic acids (GE), as well as their derivatives, show a variety of pharmacological properties. Their crystal structures provide valuable information related to the assembly modes of these biologically active compounds. In the known-to-date crystals of OA esters, their 11-oxo derivatives, and GE ester crystals, triterpenes associate, forming different types of ribbons and layers whose construction is based mainly on van der Waals forces and weak C-H···O interactions. New crystal structures of 11-oxo OA methyl ester and the polymorph of OA butyl ester reveal an alternative aggregation mode. Supramolecular architectures consist of helical chains which are stabilized by hydrogen bonds of O-H···O type. It was found that two polymorphic forms of butyl OA ester (layered and helical) are related monotropically. In a structure of metastable form, O-H···O hydrogen bonds occur, while the thermodynamically preferred phase is governed mainly by van der Waals interactions. The intermolecular interaction energies calculated using CrystalExplorer, PIXEL, and Psi4 programs showed that even in motifs formed through O-H···O hydrogen bonds, the dispersive forces have a significant impact.
Full article
(This article belongs to the Special Issue The Role of Interactions in Complexes, Clusters and Crystal Structures-Theoretical Analyses and Experimental Evidences)
►▼
Show Figures

Figure 1
Open AccessArticle
A Novel E3 Probiotics Formula Restored Gut Dysbiosis and Remodelled Gut Microbial Network and Microbiome Dysbiosis Index (MDI) in Southern Chinese Adult Psoriasis Patients
by
, , , , , , , , and
Int. J. Mol. Sci. 2023, 24(7), 6571; https://doi.org/10.3390/ijms24076571 (registering DOI) - 31 Mar 2023
Abstract
Psoriasis is a common chronic immune-mediated inflammatory skin disease with the association of various comorbidities. Despite the introduction of highly effective biologic therapies over the past few decades, the exact trigger for an immune reaction in psoriasis is unclear. With the majority of
[...] Read more.
Psoriasis is a common chronic immune-mediated inflammatory skin disease with the association of various comorbidities. Despite the introduction of highly effective biologic therapies over the past few decades, the exact trigger for an immune reaction in psoriasis is unclear. With the majority of immune cells residing in the gut, the effect of gut microbiome dysbiosis goes beyond the gastrointestinal site and may exacerbate inflammation and regulate the immune system elsewhere, including but not limited to the skin via the gut-skin axis. In order to delineate the role of the gut microbiome in Southern Chinese psoriasis patients, we performed targeted 16S rRNA sequencing and comprehensive bioinformatic analysis to compare the gut microbiome profile of 58 psoriasis patients against 49 healthy local subjects presumably with similar lifestyles. Blautia wexlerae and Parabacteroides distasonis were found to be enriched in psoriasis patients and in some of the healthy subjects, respectively. Metabolic functional pathways were predicted to be differentially abundant, with a clear shift toward SCFA synthesis in healthy subjects. The alteration of the co-occurrence network was also evident in the psoriasis group. In addition, we also profiled the gut microbiome in 52 of the 58 recruited psoriasis patients after taking 8 weeks of an orally administrated novel E3 probiotics formula (with prebiotics, probiotics and postbiotics). The Dermatological Life Quality Index (p = 0.009) and Psoriasis Area and Severity Index (p < 0.001) were significantly improved after taking 8 weeks of probiotics with no adverse effect observed. We showed that probiotics could at least partly restore gut dysbiosis via the modulation of the gut microbiome. Here, we also report the potential application of a machine learning-derived gut dysbiosis index based on a quantitative PCR panel (AUC = 0.88) to monitor gut dysbiosis in psoriasis patients. To sum up, our study suggests the gut microbial landscape differed in psoriasis patients at the genera, species, functional and network levels. Additionally, the dysbiosis index could be a cost-effective and rapid tool to monitor probiotics use in psoriasis patients.
Full article
(This article belongs to the Special Issue Atopic Dermatitis and Psoriasis Pathogenesis: Going beyond Paradigms 2.0)
Open AccessArticle
Transcriptomic Analysis of Hormone Signal Transduction, Carbohydrate Metabolism, Heat Shock Proteins, and SCF Complexes before and after Fertilization of Korean Pine Ovules
Int. J. Mol. Sci. 2023, 24(7), 6570; https://doi.org/10.3390/ijms24076570 (registering DOI) - 31 Mar 2023
Abstract
The fertilization process is a critical step in plant reproduction. However, the mechanism of action and mode of regulation of the fertilization process in gymnosperms remain unclear. In this study, we investigated the molecular regulatory networks involved in the fertilization process in Korean
[...] Read more.
The fertilization process is a critical step in plant reproduction. However, the mechanism of action and mode of regulation of the fertilization process in gymnosperms remain unclear. In this study, we investigated the molecular regulatory networks involved in the fertilization process in Korean pine ovules through anatomical observation, physiological and biochemical assays, and transcriptome sequencing technology. The morphological and physiological results indicated that fertilization proceeds through the demise of the proteinaceous vacuole, egg cell division, and pollen tube elongation. Auxin, cytokinin, soluble sugar, and soluble starch contents begin to decline upon fertilization. Transcriptomic data analysis revealed a large number of differentially expressed genes at different times before and after fertilization. These genes were primarily involved in pathways associated with plant hormone signal transduction, protein processing in the endoplasmic reticulum, fructose metabolism, and mannose metabolism. The expression levels of several key genes were further confirmed by qRT-PCR. These findings represent an important step towards understanding the mechanisms underlying morphological changes in the Korean pine ovule during fertilization, and the physiological and transcriptional analyses lay a foundation for in-depth studies of the molecular regulatory network of the Korean pine fertilization process.
Full article
(This article belongs to the Special Issue Recent Advances in Plant Molecular Science in China 2022)
Open AccessArticle
The Two-Track Investigation of Fibronectin Binding Protein A of Staphylococcus aureus from Bovine Mastitis as a Potential Candidate for Immunodiagnosis: A Pilot Study
by
, , , , , , , and
Int. J. Mol. Sci. 2023, 24(7), 6569; https://doi.org/10.3390/ijms24076569 (registering DOI) - 31 Mar 2023
Abstract
Bovine mastitis is the most common disease affecting dairy cattle worldwide and it generates substantial losses for cattle breeders. One of the most common pathogens identified in infected milk samples is Staphylococcus aureus. Currently, there is no fast test for recognizing bacteria
[...] Read more.
Bovine mastitis is the most common disease affecting dairy cattle worldwide and it generates substantial losses for cattle breeders. One of the most common pathogens identified in infected milk samples is Staphylococcus aureus. Currently, there is no fast test for recognizing bacteria species on the market. The aim of this study was to bioinformatically and laboratory detect and characterize the fibronectin binding protein A (FnBPA) of S. aureus (SA) in milk samples obtained from cows diagnosed with mastitis. More than 90,000,000 amino acid sequences were subjected to bioinformatic detection in the search for a potential biomarker for bovine SA. The analysis of FnBPA included the detection of signal peptides and nonclassical proteins, antigenicity, and the prediction of epitopes. To confirm the presence of the fnbA gene in four SA isolates, amplification with specific primers was performed. FnBPA was detected by immunoblotting. The immunoreactivity and selectivity were performed with monoclonal anti-FnBPA antibodies and SA-negative serum. The bioinformatic analysis showed that FnBPA is a surface, conservative, immunoreactive, and species-specific protein with antigenic potential. Its presence was confirmed in all of the SA isolates we studied. Immunoblotting proved its immunoreactivity and specificity. Thus, it can be considered a potential biomarker in mastitis immunodiagnostics.
Full article
(This article belongs to the Section Molecular Immunology)
Open AccessArticle
Concomitant Activation of OsNAS2 and OsNAS3 Contributes to the Enhanced Accumulation of Iron and Zinc in Rice
by
, , , , , and
Int. J. Mol. Sci. 2023, 24(7), 6568; https://doi.org/10.3390/ijms24076568 - 31 Mar 2023
Abstract
Nicotianamine (NA) is produced by NA synthase (NAS), which contains three genes in rice and is responsible for chelating metals such as iron (Fe) and zinc (Zn), as well as preserving metal homeostasis. In this study, we generated a transgenic plant (23D
[...] Read more.
Nicotianamine (NA) is produced by NA synthase (NAS), which contains three genes in rice and is responsible for chelating metals such as iron (Fe) and zinc (Zn), as well as preserving metal homeostasis. In this study, we generated a transgenic plant (23D) that shows simultaneous activation of OsNAS2 and OsNAS3 by crossing two previously identified activation-tagged mutants, OsNAS2-D1 (2D) and OsNAS3-D1 (3D). Concomitant activation of both genes resulted in the highest Fe and Zn concentrations in shoots and roots of the 23D plants grown under normal conditions and Fe and Zn limited growth conditions. Expression of genes for the biosynthesis of mugineic acid family phytosiderophores (MAs) and Fe and Zn uptake were enhanced in 23D roots. Additionally, 23D plants displayed superior growth to other plants at higher pH levels. Importantly, 23D seeds had NA and 2′-deoxymugineic acid (DMA) concentrations that were 50.6- and 10.0-fold higher than those of the WT. As a result, the mature grain Fe and Zn concentrations of the 23D plant were 4.0 and 3.5 times greater, respectively, than those of the WT. Furthermore, 23D plants exhibited the greatest resistance to excess metals. Our research suggests that simultaneous activation of OsNAS2 and OsNAS3 can enhance Fe and Zn accumulation in rice grains while also increasing plant tolerance to growing situations with metal deficiency and excess metal availability.
Full article
(This article belongs to the Special Issue Biotechnology and Crop Breeding)
Open AccessArticle
Independent Signaling of Hepatoma Derived Growth Factor and Tumor Necrosis Factor-Alpha in Human Gastric Cancer Organoids Infected by Helicobacter pylori
by
, , , , , , , , , , , , , and
Int. J. Mol. Sci. 2023, 24(7), 6567; https://doi.org/10.3390/ijms24076567 - 31 Mar 2023
Abstract
We prepared three-dimensional (3-D) organoids of human stomach cancers and examined the correlation between the tumorigenicity and cytotoxicity of Helicobacter pylori (H. pylori). In addition, the effects of hepatoma-derived growth factor (HDGF) and tumor necrosis factor (TNFα) on the growth and
[...] Read more.
We prepared three-dimensional (3-D) organoids of human stomach cancers and examined the correlation between the tumorigenicity and cytotoxicity of Helicobacter pylori (H. pylori). In addition, the effects of hepatoma-derived growth factor (HDGF) and tumor necrosis factor (TNFα) on the growth and invasion activity of H. pylori-infected gastric cancer organoids were examined. Cytotoxin-associated gene A (CagA)-green fluorescence protein (GFP)-labeled H. pylori was used to trace the infection in gastric organoids. The cytotoxicity of Cag encoded toxins from different species of H. pylori did not affect the proliferation of each H. pylori-infected cancer organoid. To clarify the role of HDGF and TNFα secreted from H. pylori-infected cancer organoids, we prepared recombinant HDGF and TNFα and measured the cytotoxicity and invasion of gastric cancer organoids. HDGF controlled the growth of each organoid in a species-specific manner of H. pylori, but TNFα decreased the cell viability in H. pylori-infected cancer organoids. Furthermore, HDGF controlled the invasion activity of H. pylori-infected cancer organoid in a species-dependent manner. However, TNFα decreased the invasion activities of most organoids. We found different signaling of cytotoxicity and invasion of human gastric organoids in response to HDGF and TNFα during infection by H. pylori. Recombinant HDGF and TNFα inhibited the development and invasion of H. pylori-infected gastric cancer differently. Thus, we propose that HDGF and TNFα are independent signals for development of H. pylori-infected gastric cancer. The signaling of growth factors in 3-D organoid culture systems is different from those in two-dimensional cancer cells.
Full article
(This article belongs to the Special Issue New Advances on Helicobacter pylori Research)
Open AccessReview
Cognitive Decline in Early and Premature Menopause
by
, , , , , , , , and
Int. J. Mol. Sci. 2023, 24(7), 6566; https://doi.org/10.3390/ijms24076566 (registering DOI) - 31 Mar 2023
Abstract
Early and premature menopause, or premature ovarian insufficiency (POI), affects 1% of women under the age of 40 years. This paper reviews the main aspects of early and premature menopause and their impact on cognitive decline. Based on the literature, cognitive complaints are
[...] Read more.
Early and premature menopause, or premature ovarian insufficiency (POI), affects 1% of women under the age of 40 years. This paper reviews the main aspects of early and premature menopause and their impact on cognitive decline. Based on the literature, cognitive complaints are more common near menopause: a phase marked by a decrease in hormone levels, especially estrogen. A premature reduction in estrogen puts women at a higher risk for cardiovascular disease, parkinsonism, depression, osteoporosis, hypertension, weight gain, midlife diabetes, as well as cognitive disorders and dementia, such as Alzheimer’s disease (AD). Experimental and epidemiological studies suggest that female sex hormones have long-lasting neuroprotective and anti-aging properties. Estrogens seem to prevent cognitive disorders arising from a cholinergic deficit in women and female animals in middle age premature menopause that affects the central nervous system (CNS) directly and indirectly, both transiently and in the long term, leads to cognitive impairment or even dementia, mainly due to the decrease in estrogen levels and comorbidity with cardiovascular risk factors, autoimmune diseases, and aging. Menopausal hormone therapy from menopause to the age of 60 years may provide a “window of opportunity” to reduce the risk of mild cognitive impairment (MCI) and AD in later life. Women with earlier menopause should be taken care of by various specialists such as gynecologists, endocrinologists, neurologists, and psychiatrists in order to maintain their mental health at the highest possible level.
Full article
(This article belongs to the Special Issue Gender-Related Molecular Mechanism in Neurological Disorders)
Open AccessArticle
Comparative Expression Profiling Reveals Molecular Markers Involved in the Progression of Cutaneous Melanoma towards Metastasis
by
, , , , and
Int. J. Mol. Sci. 2023, 24(7), 6565; https://doi.org/10.3390/ijms24076565 - 31 Mar 2023
Abstract
Cutaneous melanoma is one of the most aggressive types of cancer and often proves fatal in metastatic stages. Few treatment options are available, and its global incidence is quickly increasing. In order to gain an improved understanding of the molecular features regarding melanoma
[...] Read more.
Cutaneous melanoma is one of the most aggressive types of cancer and often proves fatal in metastatic stages. Few treatment options are available, and its global incidence is quickly increasing. In order to gain an improved understanding of the molecular features regarding melanoma progression, we have compared gene and small non-coding RNA expression profiles from cell lines derived from primary melanoma (MelJuSo), lymph node metastasis (MNT-1) and brain metastasis (VMM1), representing distinct stages of malignant progression. Our preliminary results highlighted the aberrant regulation of molecular markers involved in several processes that aid melanoma progression and metastasis development, including extracellular matrix remodeling, migratory potential and angiogenesis. Moreover, bioinformatic analysis revealed potential targets of the microRNAs of interest. Confocal microscopy and immunohistochemistry analysis were used for validation at the protein level. Exploring the molecular landscape of melanoma may contribute to the achievement of future efficient targeted therapy, as well as better prevention, diagnosis and clinical management.
Full article
(This article belongs to the Special Issue Molecular Features of Skin Cancer)
Open AccessArticle
Multiplexed Fluorescence Plate Reader In Situ Protein Expression Assay in Apoptotic HepG2 Cells
Int. J. Mol. Sci. 2023, 24(7), 6564; https://doi.org/10.3390/ijms24076564 - 31 Mar 2023
Abstract
Instead of Western blot being considered as a gold standard for intracellular protein expression assays, we developed a novel multiplexed high throughput (180 tests/day) in situ manual protein expression method directly in 96-well plates using 25,000–100,000 cells/well after formaldehyde fixation and Triton X
[...] Read more.
Instead of Western blot being considered as a gold standard for intracellular protein expression assays, we developed a novel multiplexed high throughput (180 tests/day) in situ manual protein expression method directly in 96-well plates using 25,000–100,000 cells/well after formaldehyde fixation and Triton X 100 permeabilization. HepG2 cells were treated with ochratoxin A (OTA) and staurosporine (STP) to induce apoptosis. Antioxidant and apoptotic cell signaling protein expression were studied by various rabbit primary antibodies and HRP labeled secondary antibodies. The HRP labeled immune complexes were developed by H2O2/Ampliflu Red fluorogenic reagent and measured in a plate reader. Our assay can simultaneously quantify 22 protein antigens in one plate with 4 technical replicates with an interassay imprecision of <10% CV. The fluorescence signals are referred to total intracellular protein contents in the wells and given as fluorescence/protein ratio FPR, expressed as % of the controls (FPR %). OTA caused a dose–response increase (p < 0.05–p < 0.001) in SOD2, CAT, ALB, CASP3,7,9, BCL2, BAX, Nf-kB, phospho-Erk1/2/Erk1/2, phospho-Akt/Akt, phospho-p38/p38, and phospho-PPARg/PPARg levels while phospho-AMPK/AMPK ratios decreased (p < 0.05–p < 0.001). On the contrary, STP induced a dose–response decrease (p < 0.05–p < 0.001) in CASP3,7,9, BAX, BCL2, Nf-kB and phospho-Erk1/2/Erk1/2 expression while B-ACT, phospho-Akt/Akt, phospho-p38/p38 and phospho-PPARg/PPARg ratios increased.
Full article
(This article belongs to the Collection Programmed Cell Death and Apoptosis)
Open AccessArticle
Cathepsin-L Secreted by High-Quality Bovine Embryos Exerts an Embryotrophic Effect In Vitro
by
, , , , , , , , , , , , , and
Int. J. Mol. Sci. 2023, 24(7), 6563; https://doi.org/10.3390/ijms24076563 - 31 Mar 2023
Abstract
While human in vitro embryo production is generally performed individually, animal models have shown that culturing embryos in groups improves blastocyst yield and quality. Paracrine embryotrophins could be responsible for this improved embryo development, but their identity remains largely unknown. We hypothesize that
[...] Read more.
While human in vitro embryo production is generally performed individually, animal models have shown that culturing embryos in groups improves blastocyst yield and quality. Paracrine embryotrophins could be responsible for this improved embryo development, but their identity remains largely unknown. We hypothesize that supplementation of embryotrophic proteins to a culture medium could be the key to improve individual embryo production. In this study, proteomics screening of culture media conditioned by bovine embryos revealed cathepsin-L as being secreted by both excellent- and good-quality embryos, while being absent in the medium conditioned by poor-quality embryos. The embryotrophic role of cathepsin-L was explored in vitro, whereby bovine zygotes were cultured individually for 8 days with or without cathepsin-L. Preliminary dose–response experiments pointed out 100 ng/mL as the optimal concentration of cathepsin-L in embryo culture medium. Supplementation of cathepsin-L to individual culture systems significantly improved blastocyst development and quality in terms of blastocoel formation at day 7, and the hatching ratio and apoptotic cell ratio at day 8, compared to the control. Taken together, cathepsin-L acts as an important embryotrophin by increasing embryo quality, and regulating blastulation and hatching in bovine in vitro embryo production.
Full article
(This article belongs to the Special Issue Embryonic Development and Differentiation)
Open AccessEditorial
Drought Stress Tolerance in Plants
Int. J. Mol. Sci. 2023, 24(7), 6562; https://doi.org/10.3390/ijms24076562 - 31 Mar 2023
Abstract
The current climate change scenario is accelerating degradation, desertification, and salinisation: all destructive processes that are negatively impacting arable lands and food production [...]
Full article
(This article belongs to the Special Issue Drought Stress Tolerance in Plants in 2021)
Open AccessReview
The Molecular Basis for Zinc Bioavailability
by
and
Int. J. Mol. Sci. 2023, 24(7), 6561; https://doi.org/10.3390/ijms24076561 (registering DOI) - 31 Mar 2023
Abstract
Zinc is an essential micronutrient, and its deficiency is perhaps the most prevalent and least understood worldwide. Recent advances have expanded the understanding of zinc’s unique chemistry and molecular roles in a vast array of critical functions. However, beyond the concept of zinc
[...] Read more.
Zinc is an essential micronutrient, and its deficiency is perhaps the most prevalent and least understood worldwide. Recent advances have expanded the understanding of zinc’s unique chemistry and molecular roles in a vast array of critical functions. However, beyond the concept of zinc absorption, few studies have explored the molecular basis of zinc bioavailability that determines the proportion of dietary zinc utilized in zinc-dependent processes in the body. The purpose of this review is to merge the concepts of zinc molecular biology and bioavailability with a focus on the molecular determinants of zinc luminal availability, absorption, transport, and utilization.
Full article
(This article belongs to the Special Issue Trace Elements and Minerals in Nutrition and Health)
►▼
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. 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, CIMB, IJMS, Marine Drugs, Molecules, Plants
Safety and Toxicological Risks of Medicinal Plants and Natural Products: Mechanistic Insights
Topic Editors: Eduardo Sobarzo-Sánchez, Esra Küpeli AkkolDeadline: 15 April 2023
Topic in
Biomedicines, Brain Sciences, Cells, IJMS, JCM
Applications of Biomedical Technology and Molecular Biological Approach in Brain Diseases
Topic Editors: Andrew Chih Wei Huang, Seong Soo A. An, Bai Chuang Shyu, Muh-Shi Lin, Anna KozłowskaDeadline: 30 April 2023
Topic in
Biomolecules, Cancers, Current Oncology, IJMS, Onco
Kinases in Cancer and Other Diseases
Topic Editors: Jonas Cicenas, May C. MorrisDeadline: 17 May 2023
Topic in
Cells, Diseases, IJMS, JCM, Nutrients
Proteins in Health and Diseases: New Knowledge and Practical Applications
Topic Editors: José Joaquín Cerón, Alberto Muñoz-Prieto, Vladimir Mrljak, Lorena Franco-MartinezDeadline: 31 May 2023

Conferences
Special Issues
Special Issue in
IJMS
Signaling Transduction in Cancer Metabolism
Guest Editor: BuHyun YounDeadline: 1 April 2023
Special Issue in
IJMS
Non-Coding RNAs in Human Neurodevelopmental Disorders and Brain Disorders
Guest Editors: Cristina Barbagallo, Marco RagusaDeadline: 10 April 2023
Special Issue in
IJMS
Molecular Features of Growth Factors Applied to Tissue Engineering
Guest Editor: Marco CicciuDeadline: 30 April 2023
Special Issue in
IJMS
Intercellular and Intracellular Communication in Human Health and Disease 2.0
Guest Editor: Henrique GiraoDeadline: 15 May 2023
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