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
Regulatory Role of Meox1 in Muscle Growth of Sebastes schlegelii
Int. J. Mol. Sci. 2024, 25(9), 4871; https://doi.org/10.3390/ijms25094871 (registering DOI) - 29 Apr 2024
Abstract
Meox1 is a critical transcription factor that plays a pivotal role in embryogenesis and muscle development. It has been established as a marker gene for growth-specific muscle stem cells in zebrafish. In this study, we identified the SsMeox1 gene in a large teleost
[...] Read more.
Meox1 is a critical transcription factor that plays a pivotal role in embryogenesis and muscle development. It has been established as a marker gene for growth-specific muscle stem cells in zebrafish. In this study, we identified the SsMeox1 gene in a large teleost fish, Sebastes schlegelii. Through in situ hybridization and histological analysis, we discovered that SsMeox1 can be employed as a specific marker of growth-specific muscle stem cells, which originate from the somite stage and are primarily situated in the external cell layer (ECL) and myosepta, with a minor population distributed among muscle fibers. The knockdown of SsMeox1 resulted in a significant increase in Ccnb1 expression, subsequently promoting cell cycle progression and potentially accelerating the depletion of the stem cell pool, which ultimately led to significant growth retardation. These findings suggest that SsMeox1 arrests the cell cycle of growth-specific muscle stem cells in the G2 phase by suppressing Ccnb1 expression, which is essential for maintaining the stability of the growth-specific muscle stem cell pool. Our study provides significant insights into the molecular mechanisms underlying the indeterminate growth of large teleosts.
Full article
(This article belongs to the Section Molecular Biology)
Open AccessReview
Antimicrobial Peptides towards Clinical Application—A Long History to Be Concluded
by
Laura Cresti, Giovanni Cappello and Alessandro Pini
Int. J. Mol. Sci. 2024, 25(9), 4870; https://doi.org/10.3390/ijms25094870 (registering DOI) - 29 Apr 2024
Abstract
Antimicrobial peptides (AMPs) are molecules with an amphipathic structure that enables them to interact with bacterial membranes. This interaction can lead to membrane crossing and disruption with pore formation, culminating in cell death. They are produced naturally in various organisms, including humans, animals,
[...] Read more.
Antimicrobial peptides (AMPs) are molecules with an amphipathic structure that enables them to interact with bacterial membranes. This interaction can lead to membrane crossing and disruption with pore formation, culminating in cell death. They are produced naturally in various organisms, including humans, animals, plants and microorganisms. In higher animals, they are part of the innate immune system, where they counteract infection by bacteria, fungi, viruses and parasites. AMPs can also be designed de novo by bioinformatic approaches or selected from combinatorial libraries, and then produced by chemical or recombinant procedures. Since their discovery, AMPs have aroused interest as potential antibiotics, although few have reached the market due to stability limits or toxicity. Here, we describe the development phase and a number of clinical trials of antimicrobial peptides. We also provide an update on AMPs in the pharmaceutical industry and an overall view of their therapeutic market. Modifications to peptide structures to improve stability in vivo and bioavailability are also described.
Full article
(This article belongs to the Special Issue Antimicrobial and Antiviral Peptides)
Open AccessArticle
Plasma Redox Balance in Advanced-Maternal-Age Pregnant Women and Effects of Plasma on Umbilical Cord Mesenchymal Stem Cells
by
Elena Grossini, Carmen Imma Aquino, Sakthipriyan Venkatesan, Libera Troìa, Eleonora Tizzoni, Federica Fumagalli, Daniela Ferrante, Rosanna Vaschetto, Valentino Remorgida and Daniela Surico
Int. J. Mol. Sci. 2024, 25(9), 4869; https://doi.org/10.3390/ijms25094869 (registering DOI) - 29 Apr 2024
Abstract
Pregnancy at advanced maternal age (AMA) is a condition of potential risk for the development of maternal–fetal complications with possible repercussions even in the long term. Here, we analyzed the changes in plasma redox balance and the effects of plasma on human umbilical
[...] Read more.
Pregnancy at advanced maternal age (AMA) is a condition of potential risk for the development of maternal–fetal complications with possible repercussions even in the long term. Here, we analyzed the changes in plasma redox balance and the effects of plasma on human umbilical cord mesenchymal cells (hUMSCs) in AMA pregnant women (patients) at various timings of pregnancy. One hundred patients and twenty pregnant women younger than 40 years (controls) were recruited and evaluated at various timings during pregnancy until after delivery. Plasma samples were used to measure the thiobarbituric acid reactive substances (TBARS), glutathione and nitric oxide (NO). In addition, plasma was used to stimulate the hUMSCs, which were tested for cell viability, reactive oxygen species (ROS) and NO release. The obtained results showed that, throughout pregnancy until after delivery in patients, the levels of plasma glutathione and NO were lower than those of controls, while those of TBARS were higher. Moreover, plasma of patients reduced cell viability and NO release, and increased ROS release in hUMSCs. Our results highlighted alterations in the redox balance and the presence of potentially harmful circulating factors in plasma of patients. They could have clinical relevance for the prevention of complications related to AMA pregnancy.
Full article
(This article belongs to the Special Issue Redox Homeostasis and Oxidative Stress in Human Metabolism and Disease)
Open AccessArticle
Exposure of Bladder Cancer Cells to Blue Light (l = 453 nm) in the Presence of Riboflavin Synergistically Enhances the Cytotoxic Efficiency of Gemcitabine
by
Sofia Sturm, Günter Niegisch, Joachim Windolf and Christoph V. Suschek
Int. J. Mol. Sci. 2024, 25(9), 4868; https://doi.org/10.3390/ijms25094868 (registering DOI) - 29 Apr 2024
Abstract
Non-muscle invasive bladder cancer is a common tumour in men and women. In case of resistance to the standard therapeutic agents, gemcitabine can be used as off-label instillation therapy into the bladder. To reduce potential side effects, continuous efforts are made to optimise
[...] Read more.
Non-muscle invasive bladder cancer is a common tumour in men and women. In case of resistance to the standard therapeutic agents, gemcitabine can be used as off-label instillation therapy into the bladder. To reduce potential side effects, continuous efforts are made to optimise the therapeutic potential of drugs, thereby reducing the effective dose and consequently the pharmacological burden of the medication. We recently demonstrated that it is possible to significantly increase the therapeutic efficacy of mitomycin C against a bladder carcinoma cell line by exposure to non-toxic doses of blue light (453 nm). In the present study, we investigated whether the therapeutically supportive effect of blue light can be further enhanced by the additional use of the wavelength-specific photosensitiser riboflavin. We found that the gemcitabine-induced cytotoxicity of bladder cancer cell lines (BFTC-905, SW-1710, RT-112) was significantly enhanced by non-toxic doses of blue light in the presence of riboflavin. Enhanced cytotoxicity correlated with decreased levels of mitochondrial ATP synthesis and increased lipid peroxidation was most likely the result of increased oxidative stress. Due to these properties, blue light in combination with riboflavin could represent an effective therapy option with few side effects and increase the success of local treatment of bladder cancer, whereby the dose of the chemotherapeutic agent used and thus the chemical load could be significantly reduced with similar or improved therapeutic success.
Full article
(This article belongs to the Section Molecular Oncology)
Open AccessArticle
Temperature Effects on Expression Levels of hsp Genes in Eggs and Second-Stage Juveniles of Meloidogyne hapla Chitwood, 1949
by
Łukasz Flis, Tadeusz Malewski and Renata Dobosz
Int. J. Mol. Sci. 2024, 25(9), 4867; https://doi.org/10.3390/ijms25094867 (registering DOI) - 29 Apr 2024
Abstract
Meloidogyne hapla is one of the most important nematode pathogens. It is a sedentary, biotrophic parasite of plants that overwinters in the soil or in diseased roots. The development of M. hapla is temperature dependent. Numerous studies have been performed on the effect
[...] Read more.
Meloidogyne hapla is one of the most important nematode pathogens. It is a sedentary, biotrophic parasite of plants that overwinters in the soil or in diseased roots. The development of M. hapla is temperature dependent. Numerous studies have been performed on the effect of temperature on the development of M. hapla, but only a few of them analyzed the heat shock protein (hsp) genes. The aim of the study was to perform expression profiling of eight hsp genes (Mh-hsp90, Mh-hsp1, Mh-hsp4, Mh-hsp6, Mh-hsp60, Mh-dnj19, Mh-hsp43, and Mh-hsp12.2) at two development stages of M. hapla, i.e., in eggs and second-stage juveniles (J2). The eggs and J2 were incubated under cold stress (5 °C), heat stress (35 °C, 40 °C), and non-stress (10 °C, 20 °C, and 30 °C) conditions. Expression profiling was performed by qPCR. It was demonstrated that only two genes, Mh-hsp60 and Mh-dnj19, have been upregulated by heat and cold stress at both development stages. Heat stress upregulated the expression of more hsp genes than cold stress did. The level of upregulation of most hsp genes was more marked in J2 than in eggs. The obtained results suggest that the Mh-hsp90 and Mh-hsp1 genes can be used as bioindicators of environmental impacts on nematodes of the Meloidogyne genus.
Full article
(This article belongs to the Special Issue Genes Function and Mechanism Identification in Plant Stress Resistance 3.0)
Open AccessArticle
Distinctive Nucleic Acid Recognition by Lysine-Embedded Phenanthridine Peptides
by
Josipa Matić, Patryciusz Piotrowski, Lucija Vrban, Renata Kobetić, Robert Vianello, Ivona Jurić, Ivana Fabijanić, Margareta Pernar Kovač, Anamaria Brozovic, Ivo Piantanida, Carsten Schmuck and Marijana Radić Stojković
Int. J. Mol. Sci. 2024, 25(9), 4866; https://doi.org/10.3390/ijms25094866 (registering DOI) - 29 Apr 2024
Abstract
Three new phenanthridine peptide derivatives (19, 22, and 23) were synthesized to explore their potential as spectrophotometric probes for DNA and RNA. UV/Vis and circular dichroism (CD) spectra, mass spectroscopy, and computational analysis confirmed the presence of intramolecular interactions
[...] Read more.
Three new phenanthridine peptide derivatives (19, 22, and 23) were synthesized to explore their potential as spectrophotometric probes for DNA and RNA. UV/Vis and circular dichroism (CD) spectra, mass spectroscopy, and computational analysis confirmed the presence of intramolecular interactions in all three compounds. Computational analysis revealed that compounds alternate between bent and open conformations, highlighting the latter’s crucial influence on successful polynucleotide recognition. Substituting one glycine with lysine in two regioisomers (22, 23) resulted in stronger binding interactions with DNA and RNA than for a compound containing two glycines (19), thus emphasizing the importance of lysine. The regioisomer with lysine closer to the phenanthridine ring (23) exhibited a dual and selective fluorimetric response with non-alternating AT and ATT polynucleotides and induction of triplex formation from the AT duplex. The best binding constant (K) with a value of 2.5 × 107 M−1 was obtained for the interaction with AT and ATT polynucleotides. Furthermore, apart from distinguishing between different types of ds-DNA and ds-RNA, the same compound could recognize GC-rich DNA through distinct induced CD signals.
Full article
(This article belongs to the Special Issue Computational, Structural and Spectroscopic Studies of Macromolecules)
Open AccessReview
CNS Resident Innate Immune Cells: Guardians of CNS Homeostasis
by
Luca Muzio and Jessica Perego
Int. J. Mol. Sci. 2024, 25(9), 4865; https://doi.org/10.3390/ijms25094865 (registering DOI) - 29 Apr 2024
Abstract
Although the CNS has been considered for a long time an immune-privileged organ, it is now well known that both the parenchyma and non-parenchymal tissue (meninges, perivascular space, and choroid plexus) are richly populated in resident immune cells. The advent of more
[...] Read more.
Although the CNS has been considered for a long time an immune-privileged organ, it is now well known that both the parenchyma and non-parenchymal tissue (meninges, perivascular space, and choroid plexus) are richly populated in resident immune cells. The advent of more powerful tools for multiplex immunophenotyping, such as single-cell RNA sequencing technique and upscale multiparametric flow and mass spectrometry, helped in discriminating between resident and infiltrating cells and, above all, the different spectrum of phenotypes distinguishing border-associated macrophages. Here, we focus our attention on resident innate immune players and their primary role in both CNS homeostasis and pathological neuroinflammation and neurodegeneration, two key interconnected aspects of the immunopathology of multiple sclerosis.
Full article
(This article belongs to the Special Issue Molecular Mechanism in Multiple Sclerosis and Related Disorders 2.0)
Open AccessArticle
Antiplatelet Effects of Flavonoid Aglycones Are Mediated by Activation of Cyclic Nucleotide-Dependent Protein Kinases
by
Anna Balykina, Lidia Naida, Kürsat Kirkgöz, Viacheslav O. Nikolaev, Ekaterina Fock, Michael Belyakov, Anastasiia Whaley, Andrei Whaley, Valentina Shpakova, Natalia Rukoyatkina and Stepan Gambaryan
Int. J. Mol. Sci. 2024, 25(9), 4864; https://doi.org/10.3390/ijms25094864 (registering DOI) - 29 Apr 2024
Abstract
Flavonoid aglycones are secondary plant metabolites that exhibit a broad spectrum of pharmacological activities, including anti-inflammatory, antioxidant, anticancer, and antiplatelet effects. However, the precise molecular mechanisms underlying their inhibitory effect on platelet activation remain poorly understood. In this study, we applied flow cytometry
[...] Read more.
Flavonoid aglycones are secondary plant metabolites that exhibit a broad spectrum of pharmacological activities, including anti-inflammatory, antioxidant, anticancer, and antiplatelet effects. However, the precise molecular mechanisms underlying their inhibitory effect on platelet activation remain poorly understood. In this study, we applied flow cytometry to analyze the effects of six flavonoid aglycones (luteolin, myricetin, quercetin, eriodictyol, kaempferol, and apigenin) on platelet activation, phosphatidylserine externalization, formation of reactive oxygen species, and intracellular esterase activity. We found that these compounds significantly inhibit thrombin-induced platelet activation and decrease formation of reactive oxygen species in activated platelets. The tested aglycones did not affect platelet viability, apoptosis induction, or procoagulant platelet formation. Notably, luteolin, myricetin, quercetin, and apigenin increased thrombin-induced thromboxane synthase activity, which was analyzed by a spectrofluorimetric method. Our results obtained from Western blot analysis and liquid chromatography–tandem mass spectrometry demonstrated that the antiplatelet properties of the studied phytochemicals are mediated by activation of cyclic nucleotide-dependent signaling pathways. Specifically, we established by using Förster resonance energy transfer that the molecular mechanisms are, at least partly, associated with the inhibition of phosphodiesterases 2 and/or 5. These findings underscore the therapeutic potential of flavonoid aglycones for clinical application as antiplatelet agents.
Full article
(This article belongs to the Special Issue New Advances in Thrombosis 2.0)
Open AccessArticle
Evolutionary Adaptation of an RNA Bacteriophage to Repeated Freezing and Thawing Cycles
by
Mara Laguna-Castro, Alicia Rodríguez-Moreno and Ester Lázaro
Int. J. Mol. Sci. 2024, 25(9), 4863; https://doi.org/10.3390/ijms25094863 (registering DOI) - 29 Apr 2024
Abstract
Bacteriophage fitness is determined by factors influencing both their replication within bacteria and their ability to maintain infectivity between infections. The latter becomes particularly crucial under adverse environmental conditions or when host density is low. In such scenarios, the damage experienced by viral
[...] Read more.
Bacteriophage fitness is determined by factors influencing both their replication within bacteria and their ability to maintain infectivity between infections. The latter becomes particularly crucial under adverse environmental conditions or when host density is low. In such scenarios, the damage experienced by viral particles could lead to the loss of infectivity, which might be mitigated if the virus undergoes evolutionary optimization through replication. In this study, we conducted an evolution experiment involving bacteriophage Qβ, wherein it underwent 30 serial transfers, each involving a cycle of freezing and thawing followed by replication of the surviving viruses. Our findings show that Qβ was capable of enhancing its resistance to this selective pressure through various adaptive pathways that did not impair the virus replicative capacity. Notably, these adaptations predominantly involved mutations located within genes encoding capsid proteins. The adapted populations exhibited higher resistance levels than individual viruses isolated from them, and the latter surpassed those observed in single mutants generated via site-directed mutagenesis. This suggests potential interactions among mutants and mutations. In conclusion, our study highlights the significant role of extracellular selective pressures in driving the evolution of phages, influencing both the genetic composition of their populations and their phenotypic properties.
Full article
(This article belongs to the Section Molecular Microbiology)
Open AccessArticle
Dihydrotestosterone Augments the Angiogenic and Migratory Potential of Human Endothelial Progenitor Cells by an Androgen-Dependent Mechanism
by
Mirel Adrian Popa, Cristina Maria Mihai, Viorel Iulian Șuică, Felicia Antohe, Raghvendra K. Dubey, Brigitte Leeners and Maya Simionescu
Int. J. Mol. Sci. 2024, 25(9), 4862; https://doi.org/10.3390/ijms25094862 (registering DOI) - 29 Apr 2024
Abstract
Endothelial progenitor cells (EPCs) play a critical role in cardiovascular regeneration. Enhancement of their native properties would be highly beneficial to ensuring the proper functioning of the cardiovascular system. As androgens have a positive effect on the cardiovascular system, we hypothesized that dihydrotestosterone
[...] Read more.
Endothelial progenitor cells (EPCs) play a critical role in cardiovascular regeneration. Enhancement of their native properties would be highly beneficial to ensuring the proper functioning of the cardiovascular system. As androgens have a positive effect on the cardiovascular system, we hypothesized that dihydrotestosterone (DHT) could also influence EPC-mediated repair processes. To evaluate this hypothesis, we investigated the effects of DHT on cultured human EPCs’ proliferation, viability, morphology, migration, angiogenesis, gene and protein expression, and ability to integrate into cardiac tissue. The results showed that DHT at different concentrations had no cytotoxic effect on EPCs, significantly enhanced the cell proliferation and viability and induces fast, androgen-receptor-dependent formation of capillary-like structures. DHT treatment of EPCs regulated gene expression of androgen receptors and the genes and proteins involved in cell migration and angiogenesis. Importantly, DHT stimulation promoted EPC migration and the cells’ ability to adhere and integrate into murine cardiac slices, suggesting it has a role in promoting tissue regeneration. Mass spectrometry analysis further highlighted the impact of DHT on EPCs’ functioning. In conclusion, DHT increases the proliferation, migration, and androgen-receptor-dependent angiogenesis of EPCs; enhances the cells’ secretion of key factors involved in angiogenesis; and significantly potentiates cellular integration into heart tissue. The data offer support for potential therapeutic applications of DHT in cardiovascular regeneration and repair processes.
Full article
(This article belongs to the Special Issue Exploring Stem Cell Biology for Cardiac Regeneration)
Open AccessArticle
Expression and Localization Profiles of Tight Junction Proteins in Immune Cells Depend on Their Activation Status
by
Lena Voges, Franziska Weiß, Ana-Teresa Branco, Michael Fromm and Susanne M. Krug
Int. J. Mol. Sci. 2024, 25(9), 4861; https://doi.org/10.3390/ijms25094861 (registering DOI) - 29 Apr 2024
Abstract
The ability of the immune system to combat pathogens relies on processes like antigen sampling by dendritic cells and macrophages migrating through endo- and epithelia or penetrating them with their dendrites. In addition, other immune cell subtypes also migrate through the epithelium after
[...] Read more.
The ability of the immune system to combat pathogens relies on processes like antigen sampling by dendritic cells and macrophages migrating through endo- and epithelia or penetrating them with their dendrites. In addition, other immune cell subtypes also migrate through the epithelium after activation. For paracellular migration, interactions with tight junctions (TJs) are necessary, and previous studies reported TJ protein expression in several immune cells. Our investigation aimed to characterize, in more detail, the expression profiles of TJ proteins in different immune cells in both naïve and activated states. The mRNA expression analysis revealed distinct expression patterns for TJ proteins, with notable changes, mainly increases, upon activation. At the protein level, LSR appeared predominant, being constitutively present in naïve cell membranes, suggesting roles as a crucial interaction partner. Binding experiments suggested the presence of claudins in the membrane only after stimulation, and claudin-8 translocation to the membrane occurred after stimulation. Our findings suggest a dynamic TJ protein expression in immune cells, implicating diverse functions in response to stimulation, like interaction with TJ proteins or regulatory roles. While further analysis is needed to elucidate the precise roles of TJ proteins, our findings indicate important non-canonical functions of TJ proteins in immune response.
Full article
(This article belongs to the Special Issue The Tight Junction and Its Proteins: From Structure to Pathologies)
Open AccessReview
Radiopharmaceuticals for Skeletal Muscle PET Imaging
by
Joo Yeon Park, Sun Mi Park, Tae Sup Lee, Seo Young Kang, Ji-Young Kim, Hai-Jeon Yoon, Bom Sahn Kim and Byung Seok Moon
Int. J. Mol. Sci. 2024, 25(9), 4860; https://doi.org/10.3390/ijms25094860 (registering DOI) - 29 Apr 2024
Abstract
The skeletal muscles account for approximately 40% of the body weight and are crucial in movement, nutrient absorption, and energy metabolism. Muscle loss and decline in function cause a decrease in the quality of life of patients and the elderly, leading to complications
[...] Read more.
The skeletal muscles account for approximately 40% of the body weight and are crucial in movement, nutrient absorption, and energy metabolism. Muscle loss and decline in function cause a decrease in the quality of life of patients and the elderly, leading to complications that require early diagnosis. Positron emission tomography/computed tomography (PET/CT) offers non-invasive, high-resolution visualization of tissues. It has emerged as a promising alternative to invasive diagnostic methods and is attracting attention as a tool for assessing muscle function and imaging muscle diseases. Effective imaging of muscle function and pathology relies on appropriate radiopharmaceuticals that target key aspects of muscle metabolism, such as glucose uptake, adenosine triphosphate (ATP) production, and the oxidation of fat and carbohydrates. In this review, we describe how [18F]fluoro-2-deoxy-D-glucose ([18F]FDG), [18F]fluorocholine ([18F]FCH), [11C]acetate, and [15O]water ([15O]H2O) are suitable radiopharmaceuticals for diagnostic imaging of skeletal muscles.
Full article
(This article belongs to the Special Issue Molecular Research on Skeletal Muscle Diseases)
Open AccessArticle
Molybdenum Complexes Derived from 2-Hydroxy-5-Nitrobenzaldehyde and Benzhydrazide as Potential Oxidation Catalysts and Semiconductors
by
Jana Pisk, Mia Šušković, Edi Topić, Dominique Agustin, Nenad Judaš and Luka Pavić
Int. J. Mol. Sci. 2024, 25(9), 4859; https://doi.org/10.3390/ijms25094859 (registering DOI) - 29 Apr 2024
Abstract
This study aimed to synthesize molybdenum complexes coordinated with an aroyl hydrazone-type ligand (H2L), which was generated through the condensation of 2-hydroxy-5-nitrobenzaldehyde with benzhydrazide. The synthesis yielded two types of mononuclear complexes, specifically [MoO2(L)(MeOH)] and [MoO2(L)(H2
[...] Read more.
This study aimed to synthesize molybdenum complexes coordinated with an aroyl hydrazone-type ligand (H2L), which was generated through the condensation of 2-hydroxy-5-nitrobenzaldehyde with benzhydrazide. The synthesis yielded two types of mononuclear complexes, specifically [MoO2(L)(MeOH)] and [MoO2(L)(H2O)], as well as a bipyridine-bridged dinuclear complex, [(MoO2(L))2(4,4’-bpy)]. Those entities were thoroughly characterized using a suite of analytical techniques, including attenuated total reflectance infrared spectroscopy (IR-ATR), elemental analysis (EA), thermogravimetric analysis (TGA), and single-crystal X-ray diffraction (SCXRD). Additionally, solid-state impedance spectroscopy (SS-IS) was employed to investigate the electrical properties of these complexes. The mononuclear complexes were tested as catalysts in the epoxidation of cyclooctene and the oxidation of linalool. Among these, the water-coordinated mononuclear complex, [MoO2(L)(H2O)], demonstrated superior electrical and catalytic properties. A novel contribution of this research lies in establishing a correlation between the electrical properties, structural features, and the catalytic efficiency of the complexes, marking this work as one of the pioneering studies in this area for molybdenum coordination complexes, to the best of our knowledge.
Full article
(This article belongs to the Section Materials Science)
Open AccessReview
Melatonin/Sericin Wound Healing Patches: Implications for Melanoma Therapy
by
Katarzyna Adamiak, Vivian A. Gaida, Jasmin Schäfer, Lina Bosse, Clara Diemer, Russel J. Reiter, Andrzej T. Slominski, Kerstin Steinbrink, Alina Sionkowska and Konrad Kleszczyński
Int. J. Mol. Sci. 2024, 25(9), 4858; https://doi.org/10.3390/ijms25094858 (registering DOI) - 29 Apr 2024
Abstract
Melatonin and sericin exhibit antioxidant properties and may be useful in topical wound healing patches by maintaining redox balance, cell integrity, and regulating the inflammatory response. In human skin, melatonin suppresses damage caused by ultraviolet radiation (UVR) which involves numerous mechanisms associated with
[...] Read more.
Melatonin and sericin exhibit antioxidant properties and may be useful in topical wound healing patches by maintaining redox balance, cell integrity, and regulating the inflammatory response. In human skin, melatonin suppresses damage caused by ultraviolet radiation (UVR) which involves numerous mechanisms associated with reactive oxygen species/reactive nitrogen species (ROS/RNS) generation and enhancing apoptosis. Sericin is a protein mainly composed of glycine, serine, aspartic acid, and threonine amino acids removed from the silkworm cocoon (particularly Bombyx mori and other species). It is of interest because of its biodegradability, anti-oxidative, and anti-bacterial properties. Sericin inhibits tyrosinase activity and promotes cell proliferation that can be supportive and useful in melanoma treatment. In recent years, wound healing patches containing sericin and melatonin individually have attracted significant attention by the scientific community. In this review, we summarize the state of innovation of such patches during 2021–2023. To date, melatonin/sericin-polymer patches for application in post-operational wound healing treatment has been only sparingly investigated and it is an imperative to consider these materials as a promising approach targeting for skin tissue engineering or regenerative dermatology.
Full article
(This article belongs to the Section Molecular Oncology)
Open AccessArticle
Host RNA Expression Signatures in Young Infants with Urinary Tract Infection: A Prospective Study
by
Kia Hee Schultz Dungu, Emma Louise Malchau Carlsen, Jonathan Peter Glenthøj, Lisbeth Samsø Schmidt, Inger Merete Jørgensen, Dina Cortes, Anja Poulsen, Nadja Hawwa Vissing, Frederik Otzen Bagger and Ulrikka Nygaard
Int. J. Mol. Sci. 2024, 25(9), 4857; https://doi.org/10.3390/ijms25094857 (registering DOI) - 29 Apr 2024
Abstract
Early diagnosis of infections in young infants remains a clinical challenge. Young infants are particularly vulnerable to infection, and it is often difficult to clinically distinguish between bacterial and viral infections. Urinary tract infection (UTI) is the most common bacterial infection in young
[...] Read more.
Early diagnosis of infections in young infants remains a clinical challenge. Young infants are particularly vulnerable to infection, and it is often difficult to clinically distinguish between bacterial and viral infections. Urinary tract infection (UTI) is the most common bacterial infection in young infants, and the incidence of associated bacteremia has decreased in the recent decades. Host RNA expression signatures have shown great promise for distinguishing bacterial from viral infections in young infants. This prospective study included 121 young infants admitted to four pediatric emergency care departments in the capital region of Denmark due to symptoms of infection. We collected whole blood samples and performed differential gene expression analysis. Further, we tested the classification performance of a two-gene host RNA expression signature approaching clinical implementation. Several genes were differentially expressed between young infants with UTI without bacteremia and viral infection. However, limited immunological response was detected in UTI without bacteremia compared to a more pronounced response in viral infection. The performance of the two-gene signature was limited, especially in cases of UTI without bloodstream involvement. Our results indicate a need for further investigation and consideration of UTI in young infants before implementing host RNA expression signatures in clinical practice.
Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Open AccessEditorial
Special Issue “Molecular and Cellular Advances in Atopic Diseases”
by
Beatriz Cabanillas
Int. J. Mol. Sci. 2024, 25(9), 4856; https://doi.org/10.3390/ijms25094856 (registering DOI) - 29 Apr 2024
Abstract
Atopic diseases, which currently affect around one billion people worldwide, are experiencing a rising prevalence [...]
Full article
(This article belongs to the Special Issue Molecular and Cellular Advances in Atopic Diseases)
Open AccessReview
Mitochondrial Biomarkers in the Omics Era: A Clinical-Pathophysiological Perspective
by
Jacopo Gervasoni, Aniello Primiano, Michela Cicchinelli, Lavinia Santucci, Serenella Servidei, Andrea Urbani, Guido Primiano and Federica Iavarone
Int. J. Mol. Sci. 2024, 25(9), 4855; https://doi.org/10.3390/ijms25094855 (registering DOI) - 29 Apr 2024
Abstract
Mitochondrial diseases (MDs) affect 4300 individuals, with different ages of presentation and manifestation in any organ. How defects in mitochondria can cause such a diverse range of human diseases remains poorly understood. In recent years, several published research articles regarding the metabolic and
[...] Read more.
Mitochondrial diseases (MDs) affect 4300 individuals, with different ages of presentation and manifestation in any organ. How defects in mitochondria can cause such a diverse range of human diseases remains poorly understood. In recent years, several published research articles regarding the metabolic and protein profiles of these neurogenetic disorders have helped shed light on the pathogenetic mechanisms. By investigating different pathways in MDs, often with the aim of identifying disease biomarkers, it is possible to identify molecular processes underlying the disease. In this perspective, omics technologies such as proteomics and metabolomics considered in this review, can support unresolved mitochondrial questions, helping to improve outcomes for patients.
Full article
(This article belongs to the Special Issue Proteomics and Metabonomics for Personalised Medicine)
Open AccessArticle
Gene Expression Profiling to Unfolded Proteins Response as a Risk Modulator of Patients with Rheumatoid Arthritis
by
Aleksandra Kucharska-Lusina, Maciej Skrzypek, Aleksandra Binda and Ireneusz Majsterek
Int. J. Mol. Sci. 2024, 25(9), 4854; https://doi.org/10.3390/ijms25094854 (registering DOI) - 29 Apr 2024
Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory disease. Despite new methods of diagnostics and treatment as well as extensive biological and immunosuppressive treatment, the etiology of RA is not fully understood. Moreover, the problem of diagnosis and treatment of RA patients is still
[...] Read more.
Rheumatoid arthritis (RA) is a chronic inflammatory disease. Despite new methods of diagnostics and treatment as well as extensive biological and immunosuppressive treatment, the etiology of RA is not fully understood. Moreover, the problem of diagnosis and treatment of RA patients is still current and affects a large group of patients. It is suggested that endoplasmic reticulum (ER)-related features may impair adaptation to chronic stress, inferring the risk of rheumatoid arthritis. The main goal in this study was evaluation of changes in mRNA translation to determine chronic ER stress conditions in rheumatoid arthritis patients. The study group consist of 86 individuals including a total of 56 rheumatoid arthritis patients and 30 healthy controls. The expression level of mRNA form blood samples of RA patients as well as controls of the unfolded protein response (UPR)-associated genes (p-eIF2, BCL-2, PERK, ATF4, and BAX) were investigated using real-time qPCR. GAPDH expression was used as a standard control. Considering the median, the expression levels of PERK, BCL-2, p-eIF2, ATF4, and BAX were found to be significantly increased in the blood of RA patients compared with the control group. The p-value for the PERK gene was 0.0000000036, the p-value for the BCL-2 gene was 0.000000014, the p-value for the p-eIF2 gene was 0.006948, the p-value for the ATF4 gene was 0.0000056, and the p-value for the BAX gene was 0.00019, respectively. Thus, it can be concluded that the targeting of the components of the PERK-dependent UPR signaling pathway via small-molecule PERK inhibitors may contribute to the development of novel, innovative treatment strategies against rheumatoid arthritis.
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(This article belongs to the Section Molecular Genetics and Genomics)
Open AccessArticle
Mitophagy Regulates the Circadian Rhythms by Degrading NR1D1 in Simulated Microgravity and Isolation Environments
by
Sihai Zhou, Xiaopeng Li, Fengji Liang, Guohua Ji, Ke Lv, Yanhong Yuan, Yujie Zhao, Na Yan, Chuanjie Zhang, Shiou Cai, Shuhui Zhang, Xu Liu, Bo Song and Lina Qu
Int. J. Mol. Sci. 2024, 25(9), 4853; https://doi.org/10.3390/ijms25094853 (registering DOI) - 29 Apr 2024
Abstract
Long-term spaceflight is known to induce disruptions in circadian rhythms, which are driven by a central pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus, but the underlying molecular mechanisms remain unclear. Here, we developed a rat model that simulated microgravity and
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Long-term spaceflight is known to induce disruptions in circadian rhythms, which are driven by a central pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus, but the underlying molecular mechanisms remain unclear. Here, we developed a rat model that simulated microgravity and isolation environments through tail suspension and isolation (TSI). We found that the TSI environment imposed circadian disruptions to the core body temperature, heart rate, and locomotor-activity rhythms of rats, especially in the amplitude of these rhythms. In TSI model rats’ SCNs, the core circadian gene NR1D1 showed higher protein but not mRNA levels along with decreased BMAL1 levels, which indicated that NR1D1 could be regulated through post-translational regulation. The autophagosome marker LC3 could directly bind to NR1D1 via the LC3-interacting region (LIR) motifs and induce the degradation of NR1D1 in a mitophagy-dependent manner. Defects in mitophagy led to the reversal of NR1D1 degradation, thereby suppressing the expression of BMAL1. Mitophagy deficiency and subsequent mitochondrial dysfunction were observed in the SCN of TSI models. Urolithin A (UA), a mitophagy activator, demonstrated an ability to enhance the amplitude of core body temperature, heart rate, and locomotor-activity rhythms by prompting mitophagy induction to degrade NR1D1. Cumulatively, our results demonstrate that mitophagy exerts circadian control by regulating NR1D1 degradation, revealing mitophagy as a potential target for long-term spaceflight as well as diseases with SCN circadian disruption.
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(This article belongs to the Section Molecular Neurobiology)
Open AccessArticle
Using Biotinylated Iron-Responsive Element to Analyze the Activity of Iron Regulatory Proteins
by
De-Liang Zhang, Hayden Ollivierre and Tracey A. Rouault
Int. J. Mol. Sci. 2024, 25(9), 4852; https://doi.org/10.3390/ijms25094852 (registering DOI) - 29 Apr 2024
Abstract
Iron regulatory proteins (IRP1 and IRP2) are the master regulators of mammalian iron homeostasis. They bind to the iron-responsive elements (IREs) of the transcripts of iron-related genes to regulate their expression, thereby maintaining cellular iron availability. The primary method to measure the IRE-binding
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Iron regulatory proteins (IRP1 and IRP2) are the master regulators of mammalian iron homeostasis. They bind to the iron-responsive elements (IREs) of the transcripts of iron-related genes to regulate their expression, thereby maintaining cellular iron availability. The primary method to measure the IRE-binding activity of IRPs is the electrophoresis mobility shift assay (EMSA). This method is particularly useful for evaluating IRP1 activity, since IRP1 is a bifunctional enzyme and its protein levels remain similar during conversion between the IRE-binding protein and cytosolic aconitase forms. Here, we exploited a method of using a biotinylated-IRE probe to separate IRE-binding IRPs followed by immunoblotting to analyze the IRE-binding activity. This method allows for the successful measurement of IRP activity in cultured cells and mouse tissues under various iron conditions. By separating IRE-binding IRPs from the rest of the lysates, this method increases the specificity of IRP antibodies and verifies whether a band represents an IRP, thereby revealing some previously unrecognized information about IRPs. With this method, we showed that the S711-phosphorylated IRP1 was found only in the IRE-binding form in PMA-treated Hep3B cells. Second, we found a truncated IRE-binding IRP2 isoform that is generated by proteolytic cleavage on sites in the 73aa insert region of the IRP2 protein. Third, we found that higher levels of SDS, compared to 1–2% SDS in regular loading buffer, could dramatically increase the band intensity of IRPs in immunoblots, especially in HL-60 cells. Fourth, we found that the addition of SDS or LDS to cell lysates activated protein degradation at 37 °C or room temperature, especially in HL-60 cell lysates. As this method is more practical, sensitive, and cost-effective, we believe that its application will enhance future research on iron regulation and metabolism.
Full article
(This article belongs to the Special Issue Iron Metabolism and Toxicity)
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