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
Inhibition of Amyloid-β (Aβ)-Induced Cognitive Impairment and Neuroinflammation in CHI3L1 Knockout Mice through Downregulation of ERK-PTX3 Pathway
Int. J. Mol. Sci. 2024, 25(10), 5550; https://doi.org/10.3390/ijms25105550 (registering DOI) - 19 May 2024
Abstract
Several clinical studies reported that the elevated expression of Chitinase-3-like 1 (CHI3L1) was observed in patients suffering from a wide range of diseases: cancer, metabolic, and neurological diseases. However, the role of CHI3L1 in AD is still unclear. Our previous study demonstrated that
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Several clinical studies reported that the elevated expression of Chitinase-3-like 1 (CHI3L1) was observed in patients suffering from a wide range of diseases: cancer, metabolic, and neurological diseases. However, the role of CHI3L1 in AD is still unclear. Our previous study demonstrated that 2-({3-[2-(1-Cyclohexen-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}culfanyl)-N-(4-ethylphenyl)butanamide, a CHI3L1 inhibiting compound, alleviates memory and cognitive impairment and inhibits neuroinflammation in AD mouse models. In this study, we studied the detailed correlation of CHI3L1 and AD using serum from AD patients and using CHI3L1 knockout (KO) mice with Aβ infusion (300 pmol/day, 14 days). Serum levels of CHI3L1 were significantly elevated in patients with AD compared to normal subjects, and receiver operating characteristic (ROC) analysis data based on serum analysis suggested that CHI3L1 could be a significant diagnostic reference for AD. To reveal the role of CHI3L1 in AD, we investigated the CHI3L1 deficiency effect on memory impairment in Aβ-infused mice and microglial BV-2 cells. In CHI3L1 KO mice, Aβ infusion resulted in lower levels of memory dysfunction and neuroinflammation compared to that of WT mice. CHI3L1 deficiency selectively inhibited phosphorylation of ERK and IκB as well as inhibition of neuroinflammation-related factors in vivo and in vitro. On the other hand, treatment with recombinant CHI3L1 increased neuroinflammation-related factors and promoted phosphorylation of IκB except for ERK in vitro. Web-based gene network analysis and our results showed that CHI3L1 is closely correlated with PTX3. Moreover, in AD patients, we found that serum levels of PTX3 were correlated with serum levels of CHI3L1 by Spearman correlation analysis. These results suggest that CHI3L1 deficiency could inhibit AD development by blocking the ERK-dependent PTX3 pathway.
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(This article belongs to the Topic Inflammaging: The Immunology of Aging)
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Open AccessReview
Parvalbumin Interneuron Dysfunction in Neurological Disorders: Focus on Epilepsy and Alzheimer’s Disease
by
Beulah Leitch
Int. J. Mol. Sci. 2024, 25(10), 5549; https://doi.org/10.3390/ijms25105549 (registering DOI) - 19 May 2024
Abstract
Parvalbumin expressing (PV+) GABAergic interneurons are fast spiking neurons that provide powerful but relatively short-lived inhibition to principal excitatory cells in the brain. They play a vital role in feedforward and feedback synaptic inhibition, preventing run away excitation in neural networks. Hence, their
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Parvalbumin expressing (PV+) GABAergic interneurons are fast spiking neurons that provide powerful but relatively short-lived inhibition to principal excitatory cells in the brain. They play a vital role in feedforward and feedback synaptic inhibition, preventing run away excitation in neural networks. Hence, their dysfunction can lead to hyperexcitability and increased susceptibility to seizures. PV+ interneurons are also key players in generating gamma oscillations, which are synchronized neural oscillations associated with various cognitive functions. PV+ interneuron are particularly vulnerable to aging and their degeneration has been associated with cognitive decline and memory impairment in dementia and Alzheimer’s disease (AD). Overall, dysfunction of PV+ interneurons disrupts the normal excitatory/inhibitory balance within specific neurocircuits in the brain and thus has been linked to a wide range of neurodevelopmental and neuropsychiatric disorders. This review focuses on the role of dysfunctional PV+ inhibitory interneurons in the generation of epileptic seizures and cognitive impairment and their potential as targets in the design of future therapeutic strategies to treat these disorders. Recent research using cutting-edge optogenetic and chemogenetic technologies has demonstrated that they can be selectively manipulated to control seizures and restore the balance of neural activity in the brains of animal models. This suggests that PV+ interneurons could be important targets in developing future treatments for patients with epilepsy and comorbid disorders, such as AD, where seizures and cognitive decline are directly linked to specific PV+ interneuron deficits.
Full article
(This article belongs to the Special Issue Latest Review Papers in Molecular Neurobiology 2024)
Open AccessReview
Antimicrobial Activity of Arthrospira (Former Spirulina) and Dunaliella Related to Recognized Antimicrobial Bioactive Compounds
by
Yana Ilieva, Maya Margaritova Zaharieva, Hristo Najdenski and Alexander Dimitrov Kroumov
Int. J. Mol. Sci. 2024, 25(10), 5548; https://doi.org/10.3390/ijms25105548 (registering DOI) - 19 May 2024
Abstract
With the increasing rate of the antimicrobial resistance phenomenon, natural products gain our attention as potential drug candidates. Apart from being used as nutraceuticals and for biotechnological purposes, microalgae and phytoplankton have well-recognized antimicrobial compounds and proved anti-infectious potential. In this review, we
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With the increasing rate of the antimicrobial resistance phenomenon, natural products gain our attention as potential drug candidates. Apart from being used as nutraceuticals and for biotechnological purposes, microalgae and phytoplankton have well-recognized antimicrobial compounds and proved anti-infectious potential. In this review, we comprehensively outline the antimicrobial activity of one genus of cyanobacteria (Arthrospira, formerly Spirulina) and of eukaryotic microalgae (Dunaliella). Both, especially Arthrospira, are mostly used as nutraceuticals and as a source of antioxidants for health supplements, cancer therapy and cosmetics. Their diverse bioactive compounds provide other bioactivities and potential for various medical applications. Their antibacterial and antifungal activity vary in a broad range and are strain specific. There are strains of Arthrospira platensis with very potent activity and minimum inhibitory concentrations (MICs) as low as 2–15 µg/mL against bacterial fish pathogens including Bacillus and Vibrio spp. Arthrospira sp. has demonstrated an inhibition zone (IZ) of 50 mm against Staphylococcus aureus. Remarkable is the substantial amount of in vivo studies of Arthrospira showing it to be very promising for preventing vibriosis in shrimp and Helicobacter pylori infection and for wound healing. The innovative laser irradiation of the chlorophyll it releases can cause photodynamic destruction of bacteria. Dunaliella salina has exhibited MIC values lower than 300 µg/mL and an IZ value of 25.4 mm on different bacteria, while Dunaliella tertiolecta has demonstrated MIC values of 25 and 50 μg/mL against some Staphylococcus spp. These values fulfill the criteria for significant antimicrobial activity and sometimes are comparable or exceed the activity of the control antibiotics. The bioactive compounds which are responsible for that action are fatty acids including PUFAs, polysaccharides, glycosides, peptides, neophytadiene, etc. Cyanobacteria, such as Arthrospira, also particularly have antimicrobial flavonoids, terpenes, alkaloids, saponins, quinones and some unique-to-them compounds, such as phycobiliproteins, polyhydroxybutyrate, the peptide microcystin, etc. These metabolites can be optimized by using stress factors in a two-step process of fermentation in closed photobioreactors (PBRs).
Full article
(This article belongs to the Special Issue Current Research in Antimicrobial Natural Products)
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Open AccessArticle
Neuregulin 2 Is a Candidate Gene for Autism Spectrum Disorder
by
Wei-Hsien Chien, Chia-Hsiang Chen, Min-Chih Cheng, Yu-Yu Wu and Susan Shur-Fen Gau
Int. J. Mol. Sci. 2024, 25(10), 5547; https://doi.org/10.3390/ijms25105547 (registering DOI) - 19 May 2024
Abstract
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with heterogeneous and complex genetic underpinnings. Our previous microarray gene expression profiling identified significantly different neuregulin-2 gene (NRG2) expression between ASD patients and controls. Thus, we aimed to clarify whether NRG2 is a candidate
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Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with heterogeneous and complex genetic underpinnings. Our previous microarray gene expression profiling identified significantly different neuregulin-2 gene (NRG2) expression between ASD patients and controls. Thus, we aimed to clarify whether NRG2 is a candidate gene associated with ASD. The study consisted of two stages. First, we used real-time quantitative PCR in 20 ASDs and 20 controls to confirm the microarray gene expression profiling results. The average NRG2 gene expression level in patients with ASD (3.23 ± 2.80) was significantly lower than that in the controls (9.27 ± 4.78, p < 0.001). Next, we conducted resequencing of all the exons of NRG2 in a sample of 349 individuals with ASD, aiming to identify variants of the NRG2 associated with ASD. We identified three variants, including two single nucleotide variants (SNVs), IVS3 + 13A > G (rs889022) and IVS10 + 32T > A (rs182642591), and one small deletion at exon 11 of NRG2 (delGCCCGG, rs933769137). Using data from the Taiwan Biobank as the controls, we found no significant differences in allele frequencies of rs889022 and rs182642591 between two groups. However, there is a significant difference in the genotype and allele frequency distribution of rs933769137 between ASDs and controls (p < 0.0001). The small deletion is located in the EGF-like domain at the C-terminal of the NRG2 precursor protein. Our findings suggest that NRG2 might be a susceptibility gene for ASD.
Full article
(This article belongs to the Special Issue Genetic Variations in Human Diseases)
Open AccessArticle
Safflower CtFLS1-Induced Drought Tolerance by Stimulating the Accumulation of Flavonols and Anthocyanins in Arabidopsis thaliana
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Xintong Ma, Yuying Hou, Abdul Wakeel Umar, Yuhan Wang, Lili Yu, Naveed Ahmad, Na Yao, Min Zhang and Xiuming Liu
Int. J. Mol. Sci. 2024, 25(10), 5546; https://doi.org/10.3390/ijms25105546 (registering DOI) - 19 May 2024
Abstract
Flavonol synthase gene (FLS) is a member of the 2-oxoglutarate-dependent dioxygenase (2-ODD) superfamily and plays an important role in plant flavonoids biosynthetic pathways. Safflower (Carthamus tinctorius L.), a key source of traditional Chinese medicine, is widely cultivated in
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Flavonol synthase gene (FLS) is a member of the 2-oxoglutarate-dependent dioxygenase (2-ODD) superfamily and plays an important role in plant flavonoids biosynthetic pathways. Safflower (Carthamus tinctorius L.), a key source of traditional Chinese medicine, is widely cultivated in China. Although the flavonoid biosynthetic pathway has been studied in several model species, it still remains to be explored in safflower. In this study, we aimed to elucidate the role of CtFLS1 gene in flavonoid biosynthesis and drought stress responses. The bioinformatics analysis on the CtFLS1 gene showed that it contains two FLS-specific motifs (PxxxIRxxxEQP and SxxTxLVP), suggesting its independent evolution. Further, the expression level of CtFLS1 in safflower showed a positive correlation with the accumulation level of total flavonoid content in four different flowering stages. In addition, CtFLS1-overexpression (OE) Arabidopsis plants significantly induced the expression levels of key genes involved in flavonol pathway. On the contrary, the expression of anthocyanin pathway-related genes and MYB transcription factors showed down-regulation. Furthermore, CtFLS1-OE plants promoted seed germination, as well as resistance to osmotic pressure and drought, and reduced sensitivity to ABA compared to mutant and wild-type plants. Moreover, CtFLS1 and CtANS1 were both subcellularly located at the cell membrane and nucleus; the yeast two-hybrid and bimolecular fluorescence complementation (BiFC) assay showed that they interacted with each other at the cell membrane. Altogether, these findings suggest the positive role of CtFLS1 in alleviating drought stress by stimulating flavonols and anthocyanin accumulation in safflower.
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(This article belongs to the Special Issue Nutrients and Active Substances in Natural Products)
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Open AccessArticle
Nanotechnology-Based Strategy for Enhancing Therapeutic Efficacy in Pancreatic Cancer: Receptor-Targeted Drug Delivery by Somatostatin Analog
by
Xin Gu, Joydeb Majumder, Olena Taratula, Andriy Kuzmov, Olga Garbuzenko, Natalia Pogrebnyak and Tamara Minko
Int. J. Mol. Sci. 2024, 25(10), 5545; https://doi.org/10.3390/ijms25105545 (registering DOI) - 19 May 2024
Abstract
A novel nanotechnology-based drug delivery system (DDS) targeted at pancreatic cancer cells was developed, characterized, and tested. The system consisted of liposomes as carriers, an anticancer drug (paclitaxel) as a chemotherapeutic agent, and a modified synthetic somatostatin analog, 5-pentacarbonyl-octreotide, a ligand for somatostatin
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A novel nanotechnology-based drug delivery system (DDS) targeted at pancreatic cancer cells was developed, characterized, and tested. The system consisted of liposomes as carriers, an anticancer drug (paclitaxel) as a chemotherapeutic agent, and a modified synthetic somatostatin analog, 5-pentacarbonyl-octreotide, a ligand for somatostatin receptor 2 (SSTR2), as a targeting moiety for pancreatic cancer. The cellular internalization, cytotoxicity, and antitumor activity of the DDS were tested in vitro using human pancreatic ductal adenocarcinoma (PDAC) cells with different expressions of the targeted SSTR2 receptors, and in vivo on immunodeficient mice bearing human PDAC xenografts. The targeted drug delivery system containing paclitaxel exhibited significantly enhanced cytotoxicity compared to non-targeted DDS, and this efficacy was directly related to the levels of SSTR2 expression. It was found that octreotide-targeted DDS proved exceptionally effective in suppressing the growth of PDAC tumors. This study underscores the potential of octreotide-targeted liposomal delivery systems to enhance the therapeutic outcomes for PDAC compared with non-targeted liposomal DDS and Paclitaxel-Cremophor® EL, suggesting a promising avenue for future cancer therapy innovations.
Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapies of Pancreatic Cancer)
Open AccessArticle
Superoxide Dismutase Premodulates Oxidative Stress in Plastids for Protection of Tobacco Plants from Cold Damage Ultrastructure Damage
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Ekaterina N. Baranova, Neonila V. Kononenko, Pyotr V. Lapshin, Tatiana L. Nechaeva, Marat R. Khaliluev, Natalia V. Zagoskina, Elena A. Smirnova, Natalya O. Yuorieva, Galina N. Raldugina, Inna A. Chaban, Ludmila V. Kurenina and Alexander A. Gulevich
Int. J. Mol. Sci. 2024, 25(10), 5544; https://doi.org/10.3390/ijms25105544 (registering DOI) - 19 May 2024
Abstract
ROS-dependent induction of oxidative damage can be used as a trigger initiating genetically determined non-specific protection in plant cells and tissues. Plants are potentially able to withstand various specific (toxic, osmotic) factors of abiotic effects, but do not have sufficient or specific sensitivity
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ROS-dependent induction of oxidative damage can be used as a trigger initiating genetically determined non-specific protection in plant cells and tissues. Plants are potentially able to withstand various specific (toxic, osmotic) factors of abiotic effects, but do not have sufficient or specific sensitivity to form an adequate effective response. In this work, we demonstrate one of the possible approaches for successful cold acclimation through the formation of effective protection of photosynthetic structures due to the insertion of the heterologous FeSOD gene into the tobacco genome under the control of the constitutive promoter and equipped with a signal sequence targeting the protein to plastid. The increased enzymatic activity of superoxide dismutase in the plastid compartment of transgenic tobacco plants enables them to tolerate the oxidative factor of environmental stresses scavenging ROS. On the other hand, the cost of such resistance is quite high and, when grown under normal conditions, disturbs the arrangement of the intrachloroplastic subdomains leading to the modification of stromal thylakoids, probably significantly affecting the photosynthesis processes that regulate the efficiency of photosystem II. This is partially compensated for by the fact that, at the same time, under normal conditions, the production of peroxide induces the activation of ROS detoxification enzymes. However, a violation of a number of processes, such as the metabolism of accumulation, and utilization and transportation of sugars and starch, is significantly altered, which leads to a shift in metabolic chains. The expected step for further improvement of the applied technology could be both the use of inducible promoters in the expression cassette, and the addition of other genes encoding for hydrogen peroxide-scavenging enzymes in the genetic construct that are downstream in the metabolic chain.
Full article
(This article belongs to the Special Issue Plant Adaptation Mechanism to Stress)
Open AccessReview
Therapeutic Potential of Bovine Milk-Derived Extracellular Vesicles
by
Madhusha Prasadani, Suranga Kodithuwakku, Georgia Pennarossa, Alireza Fazeli and Tiziana A. L. Brevini
Int. J. Mol. Sci. 2024, 25(10), 5543; https://doi.org/10.3390/ijms25105543 (registering DOI) - 19 May 2024
Abstract
Milk is a fundamental component of the human diet, owing to its substantial nutritional content. In addition, milk contains nanoparticles called extracellular vesicles (EVs), which have indicated their potential beneficial roles such as cell-to-cell communication, disease biomarkers, and therapeutics agents. Amidst other types
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Milk is a fundamental component of the human diet, owing to its substantial nutritional content. In addition, milk contains nanoparticles called extracellular vesicles (EVs), which have indicated their potential beneficial roles such as cell-to-cell communication, disease biomarkers, and therapeutics agents. Amidst other types of EVs, milk EVs (MEVs) have their significance due to their high abundance, easy access, and stability in harsh environmental conditions, such as low pH in the gut. There have been plenty of studies conducted to evaluate the therapeutic potential of bovine MEVs over the past few years, and attention has been given to their engineering for drug delivery and targeted therapy. However, there is a gap between the experimental findings available and clinical trials due to the many challenges related to EV isolation, cargo, and the uniformity of the material. This review aims to provide a comprehensive comparison of various techniques for the isolation of MEVs and offers a summary of the therapeutic potential of bovine MEVs described over the last decade, analyzing potential challenges and further applications. Although a number of aspects still need to be further elucidated, the available data point to the role of MEVs as a potential candidate with therapeutics potential, and the supplementation of MEVs would pave the way to understanding their in-depth effects.
Full article
(This article belongs to the Special Issue Extracellular Vesicles: The Biology and Therapeutic Applications, 2nd Edition)
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Synthesis of Novel 3-Deoxy-3-thio Derivatives of d-Glucosamine and Their Application as Ligands for the Enantioselective Addition of Diethylzinc to Benzaldehyde
by
Yusuf Zaim Hakim and Tomasz Bauer
Int. J. Mol. Sci. 2024, 25(10), 5542; https://doi.org/10.3390/ijms25105542 (registering DOI) - 19 May 2024
Abstract
A series of novel thio-derivatives of d-glucosamine has been synthesized using double inversion procedures at the C3 atom. New compounds were applied as ligands for the diethylzinc addition to benzaldehyde and the products of the addition were obtained with a low to
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A series of novel thio-derivatives of d-glucosamine has been synthesized using double inversion procedures at the C3 atom. New compounds were applied as ligands for the diethylzinc addition to benzaldehyde and the products of the addition were obtained with a low to good enantiomeric ratio. The direction and the level of the asymmetric induction were highly dependent on the type of protecting groups on the nitrogen and sulfur atoms.
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(This article belongs to the Special Issue Enantioselective Homogenous Catalysis in the Presence of Small Molecules of Natural Origin)
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Open AccessEditorial
Editorial for the Special Issue “Recent Advances in Nanomaterials Science”
by
Gang Ho Lee
Int. J. Mol. Sci. 2024, 25(10), 5541; https://doi.org/10.3390/ijms25105541 (registering DOI) - 19 May 2024
Abstract
Nanoparticles and nanomaterials are important, because they are potentially applicable to energy, storage, bioimaging, biosensors, catalysts, nanomedicine, batteries, solar energy, bioenergy, and so on (Figure 1) [...]
Full article
(This article belongs to the Special Issue Recent Advances in Nanomaterials Science)
Open AccessArticle
Antimicrobial Properties of Flavonoid Derivatives with Bromine, Chlorine, and Nitro Group Obtained by Chemical Synthesis and Biotransformation Studies
by
Martyna Perz, Daria Szymanowska, Tomasz Janeczko and Edyta Kostrzewa-Susłow
Int. J. Mol. Sci. 2024, 25(10), 5540; https://doi.org/10.3390/ijms25105540 (registering DOI) - 19 May 2024
Abstract
The search for new substances of natural origin, such as flavonoids, is necessary in the fight against the growing number of diseases and bacterial resistance to antibiotics. In our research, we wanted to check the influence of flavonoids with chlorine or bromine atoms
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The search for new substances of natural origin, such as flavonoids, is necessary in the fight against the growing number of diseases and bacterial resistance to antibiotics. In our research, we wanted to check the influence of flavonoids with chlorine or bromine atoms and a nitro group on pathogenic and probiotic bacteria. We synthesized flavonoids using Claisen–Schmidt condensation and its modifications, and through biotransformation via entomopathogenic filamentous fungi, we obtained their glycoside derivatives. Biotransformation yielded two new flavonoid glycosides: 8-amino-6-chloroflavone 4′-O-β-D-(4″-O-methyl)-glucopyranoside and 6-bromo-8-nitroflavone 4′-O-β-D-(4″-O-methyl)-glucopyranoside. Subsequently, we checked the antimicrobial properties of the aforementioned aglycon flavonoid compounds against pathogenic and probiotic bacteria and yeast. Our studies revealed that flavones have superior inhibitory effects compared to chalcones and flavanones. Notably, 6-chloro-8-nitroflavone showed potent inhibitory activity against pathogenic bacteria. Conversely, flavanones 6-chloro-8-nitroflavanone and 6-bromo-8-nitroflavanone stimulated the growth of probiotic bacteria (Lactobacillus acidophilus and Pediococcus pentosaceus). Our research has shown that the presence of chlorine, bromine, and nitro groups has a significant effect on their antimicrobial properties.
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(This article belongs to the Special Issue New Research on Bioactive Natural Products)
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Encapsulation of Nanoparticles with Statistical Copolymers with Different Surface Charges and Analysis of Their Interactions with Proteins and Cells
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Saad Megahed, Nicole Wutke, Yang Liu, Markus Klapper, Florian Schulz, Neus Feliu and Wolfgang J. Parak
Int. J. Mol. Sci. 2024, 25(10), 5539; https://doi.org/10.3390/ijms25105539 (registering DOI) - 19 May 2024
Abstract
Encapsulation with polymers is a well-known strategy to stabilize and functionalize nanomaterials and tune their physicochemical properties. Amphiphilic copolymers are promising in this context, but their structural diversity and complexity also make understanding and predicting their behavior challenging. This is particularly the case
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Encapsulation with polymers is a well-known strategy to stabilize and functionalize nanomaterials and tune their physicochemical properties. Amphiphilic copolymers are promising in this context, but their structural diversity and complexity also make understanding and predicting their behavior challenging. This is particularly the case in complex media which are relevant for intended applications in medicine and nanobiotechnology. Here, we studied the encapsulation of gold nanoparticles and quantum dots with amphiphilic copolymers differing in their charge and molecular structure. Protein adsorption to the nanoconjugates was studied with fluorescence correlation spectroscopy, and their surface activity was studied with dynamic interfacial tensiometry. Encapsulation of the nanoparticles without affecting their characteristic properties was possible with all tested polymers and provided good stabilization. However, the interaction with proteins and cells significantly depended on structural details. We identified statistical copolymers providing strongly reduced protein adsorption and low unspecific cellular uptake. Interestingly, different zwitterionic amphiphilic copolymers showed substantial differences in their resulting bio-repulsive properties. Among the polymers tested herein, statistical copolymers with sulfobetaine and phosphatidylcholine sidechains performed better than copolymers with carboxylic acid- and dimethylamino-terminated sidechains.
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(This article belongs to the Special Issue Molecular Research on Nanotoxicology)
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Gain-Type Aneuploidies Influence the Burden of Selective Long Non-Coding Transcripts in Colorectal Cancer
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Chiara Scuderi, Virginia Di Bella, Anna Provvidenza Privitera, Francesca Maria Giustolisi, Vincenza Barresi and Daniele Filippo Condorelli
Int. J. Mol. Sci. 2024, 25(10), 5538; https://doi.org/10.3390/ijms25105538 (registering DOI) - 19 May 2024
Abstract
Chromosomal instability is a hallmark of colorectal carcinogenesis and produces an accumulation of different forms of aneuploidies or broad copy number aberrations. Colorectal cancer is characterized by gain-type broad copy number aberrations, specifically in Chr20, Chr8q, Chr13 and Chr7, but their roles and
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Chromosomal instability is a hallmark of colorectal carcinogenesis and produces an accumulation of different forms of aneuploidies or broad copy number aberrations. Colorectal cancer is characterized by gain-type broad copy number aberrations, specifically in Chr20, Chr8q, Chr13 and Chr7, but their roles and mechanisms in cancer progression are not fully understood. It has been suggested that broad copy number gains might contribute to tumor development through the so-called caricature transcriptomic effect. We intend to investigate the impact of broad copy number gains on long non-coding RNAs’ expression in colorectal cancer, given their well-known role in oncogenesis. The influence of such chromosomal aberrations on lncRNAs’ transcriptome profile was investigated by SNP and transcriptome arrays in our series of colorectal cancer samples and cell lines. The correlation between aneuploidies and transcriptomic profiles led us to obtain a class of Over-UpT lncRNAs, which are transcripts upregulated in CRC and further overexpressed in colon tumors bearing specific chromosomal aberrations. The identified lncRNAs can contribute to a wide interaction network to establish the cancer driving effect of gain-type aneuploidies.
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(This article belongs to the Special Issue Transcriptional Therapy and Nucleic Acid-Based Therapeutics: From Molecular Targets to Preclinical Studies 2.0)
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Open AccessArticle
Effect of Obstructive Sleep Apnea during Pregnancy on Fetal Development: Gene Expression Profile of Cord Blood
by
Laura Cànaves-Gómez, Aarne Fleischer, Josep Muncunill-Farreny, María Paloma Gimenez, Ainhoa Álvarez Ruiz De Larrinaga, Andrés Sánchez Baron, Mercedes Codina Marcet, Mónica De-La-Peña, Daniel Morell-Garcia, José Peña Zarza, Concepción Piñas Zebrian, Susana García Fernández and Alberto Alonso
Int. J. Mol. Sci. 2024, 25(10), 5537; https://doi.org/10.3390/ijms25105537 (registering DOI) - 19 May 2024
Abstract
Obstructive sleep apnea (OSA) is quite prevalent during pregnancy and is associated with adverse perinatal outcomes, but its potential influence on fetal development remains unclear. This study investigated maternal OSA impact on the fetus by analyzing gene expression profiles in whole cord blood
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Obstructive sleep apnea (OSA) is quite prevalent during pregnancy and is associated with adverse perinatal outcomes, but its potential influence on fetal development remains unclear. This study investigated maternal OSA impact on the fetus by analyzing gene expression profiles in whole cord blood (WCB). Ten women in the third trimester of pregnancy were included, five OSA and five non-OSA cases. WCB RNA expression was analyzed by microarray technology to identify differentially expressed genes (DEGs) under OSA conditions. After data normalization, 3238 genes showed significant differential expression under OSA conditions, with 2690 upregulated genes and 548 downregulated genes. Functional enrichment was conducted using gene set enrichment analysis (GSEA) applied to Gene Ontology annotations. Key biological processes involved in OSA were identified, including response to oxidative stress and hypoxia, apoptosis, insulin response and secretion, and placental development. Moreover, DEGs were confirmed through qPCR analyses in additional WCB samples (7 with OSA and 13 without OSA). This highlighted differential expression of several genes in OSA (EGR1, PFN1 and PRKAR1A), with distinct gene expression profiles observed during rapid eye movement (REM)-OSA in pregnancy (PFN1, UBA52, EGR1, STX4, MYC, JUNB, and MAPKAP). These findings suggest that OSA, particularly during REM sleep, may negatively impact various biological processes during fetal development.
Full article
(This article belongs to the Special Issue Molecular Pathogenesis and Diagnostics of Lung Diseases)
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Open AccessReview
Genetic Modifications in Bacteria for the Degradation of Synthetic Polymers: A Review
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Diego Martín-González, Carlos de la Fuente Tagarro, Andrea De Lucas, Sergio Bordel and Fernando Santos-Beneit
Int. J. Mol. Sci. 2024, 25(10), 5536; https://doi.org/10.3390/ijms25105536 (registering DOI) - 19 May 2024
Abstract
Synthetic polymers, commonly known as plastics, are currently present in all aspects of our lives. Although they are useful, they present the problem of what to do with them after their lifespan. There are currently mechanical and chemical methods to treat plastics, but
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Synthetic polymers, commonly known as plastics, are currently present in all aspects of our lives. Although they are useful, they present the problem of what to do with them after their lifespan. There are currently mechanical and chemical methods to treat plastics, but these are methods that, among other disadvantages, can be expensive in terms of energy or produce polluting gases. A more environmentally friendly alternative is recycling, although this practice is not widespread. Based on the practice of the so-called circular economy, many studies are focused on the biodegradation of these polymers by enzymes. Using enzymes is a harmless method that can also generate substances with high added value. Novel and enhanced plastic-degrading enzymes have been obtained by modifying the amino acid sequence of existing ones, especially on their active site, using a wide variety of genetic approaches. Currently, many studies focus on the common aim of achieving strains with greater hydrolytic activity toward a different range of plastic polymers. Although in most cases the depolymerization rate is improved, more research is required to develop effective biodegradation strategies for plastic recycling or upcycling. This review focuses on a compilation and discussion of the most important research outcomes carried out on microbial biotechnology to degrade and recycle plastics.
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(This article belongs to the Special Issue Genetic Engineering in Microbial Biotechnology)
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Structure-Based De Novo Design for the Discovery of Miniprotein Inhibitors Targeting Oncogenic Mutant BRAF
by
Jae Min Ham, Myeongbin Kim, Taeho Kim, Seong Eon Ryu and Hwangseo Park
Int. J. Mol. Sci. 2024, 25(10), 5535; https://doi.org/10.3390/ijms25105535 (registering DOI) - 19 May 2024
Abstract
Being a component of the Ras/Raf/MEK/ERK signaling pathway crucial for cellular responses, the VRAF murine sarcoma viral oncogene homologue B1 (BRAF) kinase has emerged as a promising target for anticancer drug discovery due to oncogenic mutations that lead to pathway hyperactivation. Despite the
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Being a component of the Ras/Raf/MEK/ERK signaling pathway crucial for cellular responses, the VRAF murine sarcoma viral oncogene homologue B1 (BRAF) kinase has emerged as a promising target for anticancer drug discovery due to oncogenic mutations that lead to pathway hyperactivation. Despite the discovery of several small-molecule BRAF kinase inhibitors targeting oncogenic mutants, their clinical utility has been limited by challenges such as off-target effects and suboptimal pharmacological properties. This study focuses on identifying miniprotein inhibitors for the oncogenic V600E mutant BRAF, leveraging their potential as versatile drug candidates. Using a structure-based de novo design approach based on binding affinity to V600E mutant BRAF and hydration energy, 39 candidate miniprotein inhibitors comprising three helices and 69 amino acids were generated from the substructure of the endogenous ligand protein (14-3-3). Through in vitro binding and kinase inhibition assays, two miniproteins (63 and 76) were discovered as novel inhibitors of V600E mutant BRAF with low-micromolar activity, with miniprotein 76 demonstrating a specific impediment to MEK1 phosphorylation in mammalian cells. These findings highlight miniprotein 76 as a potential lead compound for developing new cancer therapeutics, and the structural features contributing to its biochemical potency against V600E mutant BRAF are discussed in detail.
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(This article belongs to the Special Issue Protein Kinase in Disease)
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Genome Variability in Artificial Allopolyploid Hybrids of Avena sativa L. and Avena macrostachya Balansa. ex Coss. et Durieu Based on Marker Sequences of Satellite DNA and the ITS1–5.8S rDNA Region
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Alexandra V. Amosova, Alexander A. Gnutikov, Alexander V. Rodionov, Igor G. Loskutov, Nikolai N. Nosov, Olga Yu. Yurkevich, Tatiana E. Samatadze, Svyatoslav A. Zoshchuk and Olga V. Muravenko
Int. J. Mol. Sci. 2024, 25(10), 5534; https://doi.org/10.3390/ijms25105534 (registering DOI) - 19 May 2024
Abstract
Artificial hybrids between cultivated Avena species and wild Avena macrostachya that possess genes for resistance to biotic and abiotic stresses can be important for oat breeding. For the first time, a comprehensive study of genomes of artificial fertile hybrids Avena sativa × Avena
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Artificial hybrids between cultivated Avena species and wild Avena macrostachya that possess genes for resistance to biotic and abiotic stresses can be important for oat breeding. For the first time, a comprehensive study of genomes of artificial fertile hybrids Avena sativa × Avena macrostachya and their parental species was carried out based on the chromosome FISH mapping of satellite DNA sequences (satDNAs) and also analysis of intragenomic polymorphism in the 18S–ITS1–5.8S rDNA region, using NGS data. Chromosome distribution patterns of marker satDNAs allowed us to identify all chromosomes in the studied karyotypes, determine their subgenomic affiliation, and detect several chromosome rearrangements. Based on the obtained cytogenomic data, we revealed differences between two A. macrostachya subgenomes and demonstrated that only one of them was inherited in the studied octoploid hybrids. Ribotype analyses showed that the second major ribotype of A. macrostachya was species-specific and was not represented in rDNA pools of the octoploids, which could be related to the allopolyploid origin of this species. Our results indicate that the use of marker satDNAs in cytogenomic studies can provide important data on genomic relationships within Avena allopolyploid species and hybrids, and also expand the potential for interspecific crosses for breeding.
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(This article belongs to the Special Issue New Insights into Satellite DNAs)
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Congenital Hyperinsulinism Caused by Mutations in ABCC8 Gene Associated with Early-Onset Neonatal Hypoglycemia: Genetic Heterogeneity Correlated with Phenotypic Variability
by
Lăcrămioara Ionela Butnariu, Delia Andreia Bizim, Gabriela Păduraru, Luminița Păduraru, Ștefana Maria Moisă, Setalia Popa, Nicoleta Gimiga, Gabriela Ghiga, Minerva Codruța Bădescu, Ancuta Lupu, Ioana Vasiliu and Laura Mihaela Trandafir
Int. J. Mol. Sci. 2024, 25(10), 5533; https://doi.org/10.3390/ijms25105533 (registering DOI) - 19 May 2024
Abstract
Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that
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Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset HH caused by ABCC8 gene mutations. In the first patient, who presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330-1)del] that correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C>T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of the focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) positron emission tomography/computed tomography (PET/CT) was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.
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(This article belongs to the Special Issue Metabolic Diseases and Genetic Variants)
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Insights into Therapeutic Response Prediction for Ustekinumab in Ulcerative Colitis Using an Ensemble Bioinformatics Approach
by
Kanellos Koustenis, Nikolas Dovrolis, Nikos Viazis, Alexandros Ioannou, Giorgos Bamias, George Karamanolis and Maria Gazouli
Int. J. Mol. Sci. 2024, 25(10), 5532; https://doi.org/10.3390/ijms25105532 (registering DOI) - 18 May 2024
Abstract
Introduction: Optimizing treatment with biological agents is an ideal goal for patients with ulcerative colitis (UC). Recent data suggest that mucosal inflammation patterns and serum cytokine profiles differ between patients who respond and those who do not. Ustekinumab, a monoclonal antibody targeting the
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Introduction: Optimizing treatment with biological agents is an ideal goal for patients with ulcerative colitis (UC). Recent data suggest that mucosal inflammation patterns and serum cytokine profiles differ between patients who respond and those who do not. Ustekinumab, a monoclonal antibody targeting the p40 subunit of interleukin (IL)-12 and IL-23, has shown promise, but predicting treatment response remains a challenge. We aimed to identify prognostic markers of response to ustekinumab in patients with active UC, utilizing information from their mucosal transcriptome. Methods: We performed a prospective observational study of 36 UC patients initiating treatment with ustekinumab. Colonic mucosal biopsies were obtained before treatment initiation for a gene expression analysis using a microarray panel of 84 inflammatory genes. A differential gene expression analysis (DGEA), correlation analysis, and network centrality analysis on co-expression networks were performed to identify potential biomarkers. Additionally, machine learning (ML) models were employed to predict treatment response based on gene expression data. Results: Seven genes, including BCL6, CXCL5, and FASLG, were significantly upregulated, while IL23A and IL23R were downregulated in non-responders compared to responders. The co-expression analysis revealed distinct patterns between responders and non-responders, with key genes like BCL6 and CRP highlighted in responders and CCL11 and CCL22 in non-responders. The ML algorithms demonstrated a high predictive power, emphasizing the significance of the IL23R, IL23A, and BCL6 genes. Conclusions: Our study identifies potential biomarkers associated with ustekinumab response in UC patients, shedding light on its underlying mechanisms and variability in treatment outcomes. Integrating transcriptomic approaches, including gene expression analyses and ML, offers valuable insights for personalized treatment strategies and highlights avenues for further research to enhance therapeutic outcomes for patients with UC.
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(This article belongs to the Section Molecular Informatics)
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The Development of a One-Step RT-qPCR for the Detection and Quantification of Viable Forms of Trypanosoma cruzi in Açai Samples from Areas at Risk of Chagas Disease through Oral Transmission
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Amanda Faier-Pereira, Paula Finamore-Araujo, Carlos Ramon do Nascimento Brito, Eldrinei Gomes Peres, Klenicy Kazumy de Lima Yamaguchi, Daniele Pereira de Castro and Otacilio C. Moreira
Int. J. Mol. Sci. 2024, 25(10), 5531; https://doi.org/10.3390/ijms25105531 (registering DOI) - 18 May 2024
Abstract
Currently, approximately 70% of new cases of Chagas disease (CD) in Brazil are attributed to oral transmission, particularly through foods such as açaí, bacaba, and sugarcane juice, primarily in the northern and northeastern regions of the country. This underscores the imperative need to
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Currently, approximately 70% of new cases of Chagas disease (CD) in Brazil are attributed to oral transmission, particularly through foods such as açaí, bacaba, and sugarcane juice, primarily in the northern and northeastern regions of the country. This underscores the imperative need to control the spread of the disease. The methods utilized to conduct quality control for food associated with outbreaks and to assess the potential for the oral transmission of CD through consuming açaí primarily rely on isolating the parasite or inoculating food into experimental animals, restricting the analyses to major research centers. While there are existing studies in the literature on the detection and quantification of T. cruzi DNA in açaí, the evaluation of parasites’ viability using molecular methods in this type of sample and differentiating between live and dead parasites in açaí pulp remain challenging. Consequently, we developed a molecular methodology based on RT-qPCR for detecting and quantifying viable T. cruzi in açaí pulp samples. This protocol enables the stabilization and preservation of nucleic acids in açaí, along with incorporating an exogenous internal amplification control. The standardization of the RNA extraction method involved a simple and reproducible approach, coupled with a one-step RT-qPCR assay. The assay underwent validation with various T. cruzi DTUs and demonstrated sensitivity in detecting up to 0.1 viable parasite equivalents/mL in açaí samples. Furthermore, we investigated the effectiveness of a bleaching method in eliminating viable parasites in açaí samples contaminated with T. cruzi by comparing the detection of DNA versus RNA. Finally, we validated this methodology using açaí pulp samples positive for T. cruzi DNA, which were collected in a municipality with a history of oral CD outbreaks (Coari-AM). This validation involved comparing the detection and quantification of total versus viable T. cruzi. Collectively, our findings demonstrate the feasibility of this methodology in detecting viable forms of T. cruzi in açaí pulp samples, emerging as a crucial tool for monitoring oral outbreaks of Chagas disease resulting from açaí consumption.
Full article
(This article belongs to the Special Issue New Strategies for the Diagnosis and Treatment of Diseases Caused by Parasites)
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