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
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
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
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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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Open AccessArticle
Insights into Therapeutic Response Prediction for Ustekinumab in Ulcerative Colitis Using an Ensemble Bioinformatics Approach
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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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Open AccessArticle
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)
Open AccessArticle
Biocompatibility Analysis of Bio-Based and Synthetic Silica Nanoparticles during Early Zebrafish Development
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Cinzia Bragato, Roberta Mazzotta, Andrea Persico, Rossella Bengalli, Mariana Ornelas, Filipa Gomes, Patrizia Bonfanti and Paride Mantecca
Int. J. Mol. Sci. 2024, 25(10), 5530; https://doi.org/10.3390/ijms25105530 (registering DOI) - 18 May 2024
Abstract
During the twenty-first century, engineered nanomaterials (ENMs) have attracted rising interest, globally revolutionizing all industrial sectors. The expanding world population and the implementation of new global policies are increasingly pushing society toward a bioeconomy, focused on fostering the adoption of bio-based nanomaterials that
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During the twenty-first century, engineered nanomaterials (ENMs) have attracted rising interest, globally revolutionizing all industrial sectors. The expanding world population and the implementation of new global policies are increasingly pushing society toward a bioeconomy, focused on fostering the adoption of bio-based nanomaterials that are functional, cost-effective, and potentially secure to be implied in different areas, the medical field included. This research was focused on silica nanoparticles (SiO2-NPs) of bio-based and synthetic origin. SiO2-NPs are composed of silicon dioxide, the most abundant compound on Earth. Due to their characteristics and biocompatibility, they are widely used in many applications, including the food industry, synthetic processes, medical diagnosis, and drug delivery. Using zebrafish embryos as in vivo models, we evaluated the effects of amorphous silica bio-based NPs from rice husk (SiO2-RHSK NPs) compared to commercial hydrophilic fumed silica NPs (SiO2-Aerosil200). We evaluated the outcomes of embryo exposure to both nanoparticles (NPs) at the histochemical and molecular levels to assess their safety profile, including developmental toxicity, neurotoxicity, and pro-inflammatory potential. The results showed differences between the two silica NPs, highlighting that bio-based SiO2-RHSK NPs do not significantly affect neutrophils, macrophages, or other innate immune system cells.
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(This article belongs to the Special Issue Zebrafish Model for Toxicological and Pharmacological Research)
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Peptides with Antimicrobial Activity in the Saliva of the Malaria Vector Anopheles coluzzii
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Giulia Bevivino, Linda Maurizi, Maria Grazia Ammendolia, Catia Longhi, Bruno Arcà and Fabrizio Lombardo
Int. J. Mol. Sci. 2024, 25(10), 5529; https://doi.org/10.3390/ijms25105529 (registering DOI) - 18 May 2024
Abstract
Mosquito saliva plays a crucial physiological role in both sugar and blood feeding by helping sugar digestion and exerting antihemostatic functions. During meal acquisition, mosquitoes are exposed to the internalization of external microbes. Since mosquitoes reingest significant amounts of saliva during feeding, we
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Mosquito saliva plays a crucial physiological role in both sugar and blood feeding by helping sugar digestion and exerting antihemostatic functions. During meal acquisition, mosquitoes are exposed to the internalization of external microbes. Since mosquitoes reingest significant amounts of saliva during feeding, we hypothesized that salivary antimicrobial components may participate in the protection of mouthparts, the crop, and the gut by inhibiting bacterial growth. To identify novel potential antimicrobials from mosquito saliva, we selected 11 candidates from Anopheles coluzzii salivary transcriptomic datasets and obtained them either using a cell-free transcription/translation expression system or, when feasible, via chemical synthesis. Hyp6.2 and hyp13, which were predicted to be produced as propeptides and cleaved in shorter mature forms, showed the most interesting results in bacterial growth inhibition assays. Hyp6.2 (putative mature form, 35 amino acid residues) significantly inhibited the growth of Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli and Serratia marcescens) bacteria. Hyp13 (short form, 19 amino acid residues) dose-dependently inhibited E. coli and S. marcescens growth, inducing membrane disruption in both Gram-positive and Gram-negative bacteria as indicated with scanning electron microscopy. In conclusion, we identified two A. coluzzii salivary peptides inhibiting Gram-positive and Gram-negative bacteria growth and possibly contributing to the protection of mosquito mouthparts and digestive tracts from microbial infection during and/or after feeding.
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(This article belongs to the Section Molecular Microbiology)
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Exacerbated Activation of the NLRP3 Inflammasome in the Placentas from Women Who Developed Chronic Venous Disease during Pregnancy
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María Asunción Sánchez-Gil, Oscar Fraile-Martinez, Cielo García-Montero, Diego De Leon-Oliva, Diego Liviu Boaru, Patricia De Castro-Martinez, Adrían Camacho-Alcázar, Juan A. De León-Luis, Coral Bravo, Raúl Díaz-Pedrero, Laura López-Gonzalez, Julia Bujan, María J. Cancelo, Melchor Álvarez-Mon, Natalio García-Honduvilla, Miguel A. Saez and Miguel A. Ortega
Int. J. Mol. Sci. 2024, 25(10), 5528; https://doi.org/10.3390/ijms25105528 (registering DOI) - 18 May 2024
Abstract
Chronic venous disease (CVD) comprises a spectrum of morphofunctional disorders affecting the venous system, affecting approximately 1 in 3 women during gestation. Emerging evidence highlights diverse maternofetal implications stemming from CVD, particularly impacting the placenta. While systemic inflammation has been associated with pregnancy-related
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Chronic venous disease (CVD) comprises a spectrum of morphofunctional disorders affecting the venous system, affecting approximately 1 in 3 women during gestation. Emerging evidence highlights diverse maternofetal implications stemming from CVD, particularly impacting the placenta. While systemic inflammation has been associated with pregnancy-related CVD, preliminary findings suggest a potential link between this condition and exacerbated inflammation in the placental tissue. Inflammasomes are major orchestrators of immune responses and inflammation in different organs and systems. Notwithstanding the relevance of inflammasomes, specifically the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3)- which has been demonstrated in the placentas of women with different obstetric complications, the precise involvement of this component in the placentas of women with CVD remains to be explored. This study employs immunohistochemistry and real-time PCR (RT-qPCR) to examine the gene and protein expression of key components in both canonical and non-canonical pathways of the NLRP3 inflammasome (NLRP3, ASC—apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain—caspase 1, caspase 5, caspase 8, and interleukin 1β) within the placental tissue of women affected by CVD. Our findings reveal a substantial upregulation of these components in CVD-affected placentas, indicating a potential pathophysiological role of the NLRP3 inflammasome in the development of this condition. Subsequent investigations should focus on assessing translational interventions addressing this dysregulation in affected patient populations.
Full article
(This article belongs to the Special Issue Translational Medicine of Vascular and Lymphatic Diseases: From the Molecule to the Clinic)
Open AccessArticle
AP2XII-1 and AP2XI-2 Suppress Schizogony Gene Expression in Toxoplasma gondii
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Yucong Jiang, Yuehong Shi, Yingying Xue, Dandan Hu and Xingju Song
Int. J. Mol. Sci. 2024, 25(10), 5527; https://doi.org/10.3390/ijms25105527 (registering DOI) - 18 May 2024
Abstract
Toxoplasma gondii is an intracellular parasite that is important in medicine and veterinary science and undergoes distinct developmental transitions in its intermediate and definitive hosts. The switch between stages of T. gondii is meticulously regulated by a variety of factors. Previous studies have
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Toxoplasma gondii is an intracellular parasite that is important in medicine and veterinary science and undergoes distinct developmental transitions in its intermediate and definitive hosts. The switch between stages of T. gondii is meticulously regulated by a variety of factors. Previous studies have explored the role of the microrchidia (MORC) protein complex as a transcriptional suppressor of sexual commitment. By utilizing immunoprecipitation and mass spectrometry, constituents of this protein complex have been identified, including MORC, Histone Deacetylase 3 (HDAC3), and several ApiAP2 transcription factors. Conditional knockout of MORC or inhibition of HDAC3 results in upregulation of a set of genes associated with schizogony and sexual stages in T. gondii tachyzoites. Here, our focus extends to two primary ApiAP2s (AP2XII-1 and AP2XI-2), demonstrating their significant impact on the fitness of asexual tachyzoites and their target genes. Notably, the targeted disruption of AP2XII-1 and AP2XI-2 resulted in a profound alteration in merozoite-specific genes targeted by the MORC–HDAC3 complex. Additionally, considerable overlap was observed in downstream gene profiles between AP2XII-1 and AP2XI-2, with AP2XII-1 specifically binding to a subset of ApiAP2 transcription factors, including AP2XI-2. These findings reveal an intricate cascade of ApiAP2 regulatory networks involved in T. gondii schizogony development, orchestrated by AP2XII-1 and AP2XI-2. This study provides valuable insights into the transcriptional regulation of T. gondii growth and development, shedding light on the intricate life cycle of this parasitic pathogen.
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(This article belongs to the Collection Feature Papers in Molecular Microbiology)
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Accumulation of Alpha-Synuclein and Increase in the Inflammatory Response in the substantia nigra, Jejunum, and Colon in a Model of O3 Pollution in Rats
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Marlen Valdés-Fuentes, Erika Rodríguez-Martínez and Selva Rivas-Arancibia
Int. J. Mol. Sci. 2024, 25(10), 5526; https://doi.org/10.3390/ijms25105526 (registering DOI) - 18 May 2024
Abstract
This work aimed to study the effect of repeated exposure to low doses of ozone on alpha-synuclein and the inflammatory response in the substantia nigra, jejunum, and colon. Seventy-two male Wistar rats were divided into six groups. Each group received one of the
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This work aimed to study the effect of repeated exposure to low doses of ozone on alpha-synuclein and the inflammatory response in the substantia nigra, jejunum, and colon. Seventy-two male Wistar rats were divided into six groups. Each group received one of the following treatments: The control group was exposed to air. The ozone groups were exposed for 7, 15, 30, 60, and 90 days for 0.25 ppm for four hours daily. Afterward, they were anesthetized, and their tissues were extracted and processed using Western blotting, immunohistochemistry, and qPCR. The results indicated a significant increase in alpha-synuclein in the substantia nigra and jejunum from 7 to 60 days of exposure and an increase in NFκB from 7 to 90 days in the substantia nigra, while in the jejunum, a significant increase was observed at 7 and 15 days and a decrease at 60 and 90 days for the colon. Interleukin IL-17 showed an increase at 90 days in the substantia nigra in the jejunum and increases at 30 days and in the colon at 15 and 90 days. Exposure to ozone increases the presence of alpha-synuclein and induces the loss of regulation of the inflammatory response, which contributes significantly to degenerative processes.
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(This article belongs to the Special Issue Environmentally Induced Oxidative Stress Toxicology)
Open AccessArticle
A Well-Established Gut Microbiota Enhances the Efficiency of Nutrient Metabolism and Improves the Growth Performance of Trachinotus ovatus
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Miao Kong, Wendong Zhao, Cong Wang, Jie Qi, Jinxiang Liu and Quanqi Zhang
Int. J. Mol. Sci. 2024, 25(10), 5525; https://doi.org/10.3390/ijms25105525 (registering DOI) - 18 May 2024
Abstract
The gut microbiota has become an essential component of the host organism and plays a crucial role in the host immune system, metabolism, and physiology. Nevertheless, our comprehension of how the fish gut microbiota contributes to enhancing nutrient utilization in the diet and
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The gut microbiota has become an essential component of the host organism and plays a crucial role in the host immune system, metabolism, and physiology. Nevertheless, our comprehension of how the fish gut microbiota contributes to enhancing nutrient utilization in the diet and improving host growth performance remains unclear. In this study, we employed a comprehensive analysis of the microbiome, metabolome, and transcriptome to analyze intestines of the normal control group and the antibiotic-treated model group of T. ovatus to investigate how the gut microbiota enhances fish growth performance and uncover the underlying mechanisms. First, we found that the growth performance of the control group was significantly higher than that of the antibiotic-treated model under the same feeding conditions. Subsequent multiomics analyses showed that the gut microbiota can improve its own composition by mediating the colonization of some probiotics represented by Lactobacillus in the intestine, improving host metabolic efficiency with proteins and lipids, and also influencing the expression of genes in signaling pathways related to cell proliferation, which together contribute to the improved growth performance of T. ovatus. Our results demonstrated the important contribution of gut microbiota and its underlying molecular mechanisms on the growth performance of T. ovatus.
Full article
(This article belongs to the Special Issue Microbial Omics)
Open AccessArticle
High-Caloric Diets in Adolescence Impair Specific GABAergic Subpopulations, Neurogenesis, and Alter Astrocyte Morphology
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Bárbara Mota, Ana Rita Brás, Leonardo Araújo-Andrade, Ana Silva, Pedro A. Pereira, M. Dulce Madeira and Armando Cardoso
Int. J. Mol. Sci. 2024, 25(10), 5524; https://doi.org/10.3390/ijms25105524 (registering DOI) - 18 May 2024
Abstract
We compared the effects of two different high-caloric diets administered to 4-week-old rats for 12 weeks: a diet rich in sugar (30% sucrose) and a cafeteria diet rich in sugar and high-fat foods. We focused on the hippocampus, particularly on the gamma-aminobutyric acid
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We compared the effects of two different high-caloric diets administered to 4-week-old rats for 12 weeks: a diet rich in sugar (30% sucrose) and a cafeteria diet rich in sugar and high-fat foods. We focused on the hippocampus, particularly on the gamma-aminobutyric acid (GABA)ergic system, including the Ca2+-binding proteins parvalbumin (PV), calretinin (CR), calbindin (CB), and the neuropeptides somatostatin (SST) and neuropeptide Y (NPY). We also analyzed the density of cholinergic varicosities, brain-derived neurotrophic factor (BDNF), reelin (RELN), and cyclin-dependent kinase-5 (CDK-5) mRNA levels, and glial fibrillary acidic protein (GFAP) expression. The cafeteria diet reduced PV-positive neurons in the granular layer, hilus, and CA1, as well as NPY-positive neurons in the hilus, without altering other GABAergic populations or overall GABA levels. The high-sugar diet induced a decrease in the number of PV-positive cells in CA3 and an increase in CB-positive cells in the hilus and CA1. No alterations were observed in the cholinergic varicosities. The cafeteria diet also reduced the relative mRNA expression of RELN without significant changes in BDNF and CDK5 levels. The cafeteria diet increased the number but reduced the length of the astrocyte processes. These data highlight the significance of determining the mechanisms mediating the observed effects of these diets and imply that the cognitive impairments previously found might be related to both the neuroinflammation process and the reduction in PV, NPY, and RELN expression in the hippocampal formation.
Full article
(This article belongs to the Special Issue Focus on Hippocampus Biology: From Neurophysiology to Dysfunctions)
Open AccessArticle
Sustainable and Safe N-alkylation of N-heterocycles by Propylene Carbonate under Neat Reaction Conditions
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Andrea Czompa, Dóra Bogdán, Balázs Balogh, Eszter Erdei, Patrik Selymes, Attila Csomos and István M. Mándity
Int. J. Mol. Sci. 2024, 25(10), 5523; https://doi.org/10.3390/ijms25105523 (registering DOI) - 18 May 2024
Abstract
A new, eco-friendly process utilising the green solvent propylene carbonate (PC) has been developed to perform N-alkylation of N-, O- and/or S-containing heterocyclic compounds. PC in these reactions served as both the reagent and solvent. Importantly, no genotoxic alkyl
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A new, eco-friendly process utilising the green solvent propylene carbonate (PC) has been developed to perform N-alkylation of N-, O- and/or S-containing heterocyclic compounds. PC in these reactions served as both the reagent and solvent. Importantly, no genotoxic alkyl halides were required. No auxiliary was necessary when using anhydrous PC. Product formation includes nucleophilic substitution with the concomitant loss of water and carbon dioxide. Substrates prepared, including the newly invented PROTAC drugs, are widely used.
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(This article belongs to the Special Issue Recent Advances in Organic Chemistry: Molecules Synthesis and Reactions)
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Isolation and Characterization of Cell-Free DNA from Cerebral Organoids
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Brian B. Silver, Ashley Brooks, Kevin Gerrish and Erik J. Tokar
Int. J. Mol. Sci. 2024, 25(10), 5522; https://doi.org/10.3390/ijms25105522 (registering DOI) - 18 May 2024
Abstract
Early detection of neurological conditions is critical for timely diagnosis and treatment. Identifying cellular-level changes is essential for implementing therapeutic interventions prior to symptomatic disease onset. However, monitoring brain tissue directly through biopsies is invasive and poses a high risk. Bodily fluids such
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Early detection of neurological conditions is critical for timely diagnosis and treatment. Identifying cellular-level changes is essential for implementing therapeutic interventions prior to symptomatic disease onset. However, monitoring brain tissue directly through biopsies is invasive and poses a high risk. Bodily fluids such as blood or cerebrospinal fluid contain information in many forms, including proteins and nucleic acids. In particular, cell-free DNA (cfDNA) has potential as a versatile neurological biomarker. Yet, our knowledge of cfDNA released by brain tissue and how cfDNA changes in response to deleterious events within the brain is incomplete. Mapping changes in cfDNA to specific cellular events is difficult in vivo, wherein many tissues contribute to circulating cfDNA. Organoids are tractable systems for examining specific changes consistently in a human background. However, few studies have investigated cfDNA released from organoids. Here, we examined cfDNA isolated from cerebral organoids. We found that cerebral organoids release quantities of cfDNA sufficient for downstream analysis with droplet-digital PCR and whole-genome sequencing. Further, gene ontology analysis of genes aligning with sequenced cfDNA fragments revealed associations with terms related to neurodevelopment and autism spectrum disorder. We conclude that cerebral organoids hold promise as tools for the discovery of cfDNA biomarkers related to neurodevelopmental and neurological disorders.
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(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Open AccessEditorial
Overcoming Biological Barriers: Importance of Membrane Transporters in Homeostasis, Disease, and Disease Treatment 2.0
by
Giuliano Ciarimboli
Int. J. Mol. Sci. 2024, 25(10), 5521; https://doi.org/10.3390/ijms25105521 (registering DOI) - 18 May 2024
Abstract
This editorial summarizes the seven scientific papers published in the Special Issue “Overcoming Biological Barriers: Importance of Membrane Transporters in Homeostasis, Disease, and Disease Treatment 2 [...]
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(This article belongs to the Special Issue Overcoming Biological Barriers: Importance of Membrane Transporters in Homeostasis, Disease, and Disease Treatment 2.0)
Open AccessArticle
Molecular Orientation Behavior of Lyotropic Liquid Crystal–Carbon Dot Hybrids in Microfluidic Confinement
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Artem Bezrukov, Aliya Galeeva, Aleksandr Krupin and Yuriy Galyametdinov
Int. J. Mol. Sci. 2024, 25(10), 5520; https://doi.org/10.3390/ijms25105520 (registering DOI) - 18 May 2024
Abstract
Lyotropic liquid crystals represent an important class of anisotropic colloid systems. Their integration with optically active nanoparticles can provide us with responsive luminescent media that offer new fundamental and applied solutions for biomedicine. This paper analyzes the molecular-level behavior of such composites represented
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Lyotropic liquid crystals represent an important class of anisotropic colloid systems. Their integration with optically active nanoparticles can provide us with responsive luminescent media that offer new fundamental and applied solutions for biomedicine. This paper analyzes the molecular-level behavior of such composites represented by tetraethylene glycol monododecyl ether and nanoscale carbon dots in microfluidic channels. Microfluidic confinement allows for simultaneously applying multiple factors, such as flow dynamics, wall effects, and temperature, for the precise control of the molecular arrangement in such composites and their resulting optical properties. The microfluidic behavior of composites was characterized by a set of analytical and modeling tools such as polarized and fluorescent microscopy, dynamic light scattering, and fluorescent spectroscopy, as well as image processing in Matlab. The composites were shown to form tunable anisotropic intermolecular structures in microchannels with several levels of molecular ordering. A predominant lamellar structure of the composites was found to undergo additional ordering with respect to the microchannel axis and walls. Such an alignment was controlled by applying shear and temperature factors to the microfluidic environment. The revealed molecular behavior of the composite may contribute to the synthesis of hybrid organized media capable of polarized luminescence for on-chip diagnostics and biomimetics.
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(This article belongs to the Section Physical Chemistry and Chemical Physics)
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Open AccessArticle
Cytosine Deaminase-Overexpressing hTERT-Immortalized Human Adipose Stem Cells Enhance the Inhibitory Effects of Fluorocytosine on Tumor Growth in Castration Resistant Prostate Cancer
by
Jae Heon Kim, Hee Jo Yang, Sang Hun Lee and Yun Seob Song
Int. J. Mol. Sci. 2024, 25(10), 5519; https://doi.org/10.3390/ijms25105519 (registering DOI) - 18 May 2024
Abstract
A promising de novo approach for the treatment of Castration-resistant prostate cancer (CRPC) exploits cell-mediated enzyme prodrug therapy comprising cytosine deaminase (CD) and fluorouracil (5-FC). The aim of this study was to determine the potential of bacterial CD-overexpressing hTERT-immortalized human adipose stem cells
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A promising de novo approach for the treatment of Castration-resistant prostate cancer (CRPC) exploits cell-mediated enzyme prodrug therapy comprising cytosine deaminase (CD) and fluorouracil (5-FC). The aim of this study was to determine the potential of bacterial CD-overexpressing hTERT-immortalized human adipose stem cells (hTERT-ADSC.CD) to suppress CRPC. A lentiviral vector encoding a bacterial CD gene was used to transfect and to generate the hTERT-ADSC.CD line. The ability of the cells to migrate selectively towards malignant cells was investigated in vitro. PC3 and hTERT-ADSC.CD cells were co-cultured in order to establish. hTERT-ADSC.CD and 1 × 106 PC3 cells were administered to nude mice via intracardiac and subcutaneous injections, respectively, and 5-FC was given for 14 days. hTERT-ADSC.CD were successfully engineered. Enhanced in vitro hTERT-ADSC.CD cytotoxicity and suicide effect were evident following administration of 5 μM 5-FC. hTERT-ADSC.CD, together with 5-FC, augmented the numbers of PC3 cells undergoing apoptosis. In comparison to controls administered hTERT-ADSC.CD monotherapy, hTERT-ADSC.CD in combination with 5-FC demonstrated a greater suppressive effect on tumor. In CPRC-bearing mice, tumor suppression was enhanced by the combination of CD-overexpressing ADSC and the prodrug 5-FC. Stem cells exhibiting CD gene expression are a potential novel approach to treatment for CRPC.
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(This article belongs to the Special Issue Cancer Suicide Gene Therapy)
Open AccessArticle
Differential Transcription Profiling Reveals the MicroRNAs Involved in Alleviating Damage to Photosynthesis under Drought Stress during the Grain Filling Stage in Wheat
by
Ruixiang Zhou, Yuhang Song, Xinyu Xue, Ruili Xue, Haifang Jiang, Yi Zhou, Xueli Qi and Yuexia Wang
Int. J. Mol. Sci. 2024, 25(10), 5518; https://doi.org/10.3390/ijms25105518 (registering DOI) - 18 May 2024
Abstract
To explore the possible novel microRNA (miRNA) regulatory pathways in Zhengmai 1860, a newly cultivated drought-tolerant wheat (Triticum aestivum L.) cultivar, miRNA transcriptome sequencing of the flag leaves of Zhengmai 1860, drought-sensitive variety Zhoumai 18, and drought-resistant variety Bainong 207 was performed
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To explore the possible novel microRNA (miRNA) regulatory pathways in Zhengmai 1860, a newly cultivated drought-tolerant wheat (Triticum aestivum L.) cultivar, miRNA transcriptome sequencing of the flag leaves of Zhengmai 1860, drought-sensitive variety Zhoumai 18, and drought-resistant variety Bainong 207 was performed during the grain filling stage. We also observed changes in the chloroplast ultrastructure, phytohormone levels, and antioxidant- and photosynthesis-related physiological indicators in three wheat varieties. The results showed that the flag leaves of the drought-tolerant variety Zhengmai 1860 had higher chlorophyll contents and net photosynthetic rates than those of Zhoumai 18 under drought stress during the grain filling stage; in addition, the chloroplast structure was more complete. However, there was no significant difference between Zhengmai 1860 and Bainong 207. MiRNA transcriptome analysis revealed that the differential expression of the miRNAs and mRNAs exhibited variable specificity. The KEGG pathway enrichment results indicated that most of the genes were enriched in the MAPK signaling pathway, plant hormone signal transduction, photosynthetic antennae protein, and amino acid and carbohydrate metabolism. In the drought-tolerant cultivar Zhengmai 1860, tae-miR408 was targeted to regulate the allene oxide synthase (AOS) gene, inhibit its expression, reduce the AOS content, and decrease the synthesis of jasmonic acid (JA) and abscisic acid (ABA). The results of this study suggest that Zhengmai 1860 could improve the photosynthetic performance of flag leaves by inhibiting the expression of genes involved in the JA pathway through miRNAs under drought conditions. Moreover, multiple miRNAs may target chlorophyll, antioxidant enzymes, phytohormone signal transduction, and other related pathways; thus, it is possible to provide a more theoretical basis for wheat molecular breeding.
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(This article belongs to the Special Issue Plant Physiology and Molecular Nutrition)
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Combined Metabolite and Transcriptomic Profiling Unveil a Potential Gene Network Involved in the Triterpenoid Metabolism of Rose roxburghii
by
Liangqun Li, Mei Peng, Yanfang Yan, Tingfei Deng, Qiancheng Liang, Xian Tao, Haodong Li, Juan Yang, Guandi He, Sanwei Yang, Xiaojun Pu and Xiaosheng Yang
Int. J. Mol. Sci. 2024, 25(10), 5517; https://doi.org/10.3390/ijms25105517 (registering DOI) - 18 May 2024
Abstract
Rose roxburghii, a horticulturally significant species within the Rosa genus of the Rosaceae family, is renowned for its abundance of secondary metabolites and ascorbate, earning it the title ‘king of vitamin C’. Despite this recognition, the mechanisms underlying the biosynthesis and regulation
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Rose roxburghii, a horticulturally significant species within the Rosa genus of the Rosaceae family, is renowned for its abundance of secondary metabolites and ascorbate, earning it the title ‘king of vitamin C’. Despite this recognition, the mechanisms underlying the biosynthesis and regulation of triterpenoid compounds in R. roxburghii remain largely unresolved. In this study, we conducted high-performance liquid chromatography profiling across various organs of R. roxburghii, including fruit, root, stem, and leaves, revealing distinct distributions of triterpenoid compounds among different plant parts. Notably, the fruit exhibited the highest total triterpenoid content, followed by root and stem, with leaf containing the lowest levels, with leaf containing the lowest levels. Transcriptomic analysis unveiled preferential expression of members from the cytochrome P450 (CYP) and glycosyltransferase (UGT) families, likely contributing to the higher accumulation of both ascorbate and triterpenoid compounds in the fruits of R. roxburghii compared to other tissues of R. roxburghii. Transcriptomic analysis unveiled a potential gene network implicated in the biosynthesis of both ascorbate and triterpenoid compounds in R. roxburghii. These findings not only deepen our understanding of the metabolic pathways in this species but also have implications for the design of functional foods enriched with ascorbate and triterpenoids in R. roxburghii.
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(This article belongs to the Special Issue Advance in Plant Abiotic Stress)
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Fatty Acids and Their Lipogenic Enzymes in Anorexia Nervosa Clinical Subtypes
by
Nhien Nguyen, D. Blake Woodside, Eileen Lam, Oswald Quehenberger, J. Bruce German and Pei-an Betty Shih
Int. J. Mol. Sci. 2024, 25(10), 5516; https://doi.org/10.3390/ijms25105516 (registering DOI) - 18 May 2024
Abstract
Disordered eating behavior differs between the restricting subtype (AN-R) and the binging and purging subtype (AN-BP) of anorexia nervosa (AN). Yet, little is known about how these differences impact fatty acid (FA) dysregulation in AN. To address this question, we analyzed 26 FAs
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Disordered eating behavior differs between the restricting subtype (AN-R) and the binging and purging subtype (AN-BP) of anorexia nervosa (AN). Yet, little is known about how these differences impact fatty acid (FA) dysregulation in AN. To address this question, we analyzed 26 FAs and 7 FA lipogenic enzymes (4 desaturases and 3 elongases) in 96 women: 25 AN-R, 25 AN-BP, and 46 healthy control women. Our goal was to assess subtype-specific patterns. Lauric acid was significantly higher in AN-BP than in AN-R at the fasting timepoint (p = 0.038) and displayed significantly different postprandial changes 2 h after eating. AN-R displayed significantly higher levels of n-3 alpha-linolenic acid, stearidonic acid, eicosapentaenoic acid (EPA), docosapentaenoic acid, and n-6 linoleic acid and gamma-linolenic acid compared to controls. AN-BP showed elevated EPA and saturated lauric acid compared to controls. Higher EPA was associated with elevated anxiety in AN-R (p = 0.035) but was linked to lower anxiety in AN-BP (p = 0.043). These findings suggest distinct disordered eating behaviors in AN subtypes contribute to lipid dysregulation and eating disorder comorbidities. A personalized dietary intervention may improve lipid dysregulation and enhance treatment effectiveness for AN.
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(This article belongs to the Special Issue Lipid Metabolism in Human Diseases)
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The Long Non-Coding RNA MALAT1 Modulates NR4A1 Expression through a Downstream Regulatory Element in Specific Cancer Cell Types
by
Sara Wernig-Zorc, Uwe Schwartz, Paulina Martínez-Rodríguez, Josefa Inalef, Francisca Pavicic, Pamela Ehrenfeld, Gernot Längst and Rodrigo Maldonado
Int. J. Mol. Sci. 2024, 25(10), 5515; https://doi.org/10.3390/ijms25105515 (registering DOI) - 18 May 2024
Abstract
Long non-coding RNAs (lncRNAs) have been shown to modulate gene expression and are involved in the initiation and progression of various cancer types. Despite the wealth of studies describing transcriptome changes upon lncRNA knockdown, there is limited information describing lncRNA-mediated effects on regulatory
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Long non-coding RNAs (lncRNAs) have been shown to modulate gene expression and are involved in the initiation and progression of various cancer types. Despite the wealth of studies describing transcriptome changes upon lncRNA knockdown, there is limited information describing lncRNA-mediated effects on regulatory elements (REs) modulating gene expression. In this study, we investigated how the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) lncRNA regulates primary target genes using time-resolved MALAT1 knockdown followed by parallel RNA-seq and ATAC-seq assays. The results revealed that MALAT1 primarily regulates specific protein-coding genes and a substantial decrease in the accessibility downstream of the NR4A1 gene that was associated with a decreased NR4A1 expression. Moreover, the presence of an NR4A1-downstream RE was demonstrated by CRISPR-i assays to define a functional MALAT1/NR4A1 axis. By analyzing TCGA data, we identified a positive correlation between NR4A1 expression and NR4A1-downstream RE accessibility in breast cancer but not in pancreatic cancer. Accordingly, this regulatory mechanism was experimentally validated in breast cancer cells (MCF7) but not in pancreatic duct epithelial carcinoma (PANC1) cells. Therefore, our results demonstrated that MALAT1 is involved in a molecular mechanism that fine-tunes NR4A1 expression by modulating the accessibility of a downstream RE in a cell type-specific manner.
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(This article belongs to the Special Issue Pathways in Development and Disease: The Role of RNA Regulation in Biological and Pathological Events)
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