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
Specific Extracellular Vesicles, Generated and Operating at Synapses, Contribute to Neuronal Effects and Signaling
Int. J. Mol. Sci. 2024, 25(10), 5103; https://doi.org/10.3390/ijms25105103 (registering DOI) - 07 May 2024
Abstract
In all cell types, small EVs, very abundant extracellular vesicles, are generated and accumulated within MVB endocytic cisternae. Upon MVB fusion and exocytosis with the plasma membrane, the EVs are released to the extracellular space. In the central nervous system, the release of
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In all cell types, small EVs, very abundant extracellular vesicles, are generated and accumulated within MVB endocytic cisternae. Upon MVB fusion and exocytosis with the plasma membrane, the EVs are released to the extracellular space. In the central nervous system, the release of neuronal EVs was believed to occur only from the surface of the body and dendrites. About 15 years ago, MVB cisternae and EVs were shown to exist and function at synaptic boutons, the terminals’ pre- and post-synaptic structures essential for canonical neurotransmitter release. Recent studies have revealed that synaptic EVs are peculiar in many respects and heterogeneous with respect to other neuronal EVs. The distribution of synaptic EVs and the effect of their specific molecules are found at critical sites of their distribution. The role of synaptic EVs could consist of the modulation of canonical neurotransmitter release or a distinct, non-canonical form of neurotransmission. Additional roles of synaptic EVs are still not completely known. In the future, additional investigations will clarify the role of synaptic EVs in pathology, concerning, for example, circuits, trans-synaptic transmission, diagnosis and the therapy of diseases.
Full article
(This article belongs to the Special Issue Exosomes and Extracellular Vesicles in Health and Diseases 2.0)
Open AccessArticle
Customizing EV-CATCHER to Purify Placental Extracellular Vesicles from Maternal Plasma to Detect Placental Pathologies
by
Megan I. Mitchell, Marwa Khalil, Iddo Z. Ben-Dov, Jesus Alverez-Perez, Nicholas P. Illsley, Stacy Zamudio, Abdulla Al-Khan and Olivier Loudig
Int. J. Mol. Sci. 2024, 25(10), 5102; https://doi.org/10.3390/ijms25105102 (registering DOI) - 07 May 2024
Abstract
Placenta Accreta Spectrum (PAS) is a life-threatening condition in which placental trophoblastic cells abnormally invade the uterus, often up to the uterine serosa and, in extreme cases, tissues beyond the uterine wall. Currently, there is no clinical assay for the non-invasive detection of
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Placenta Accreta Spectrum (PAS) is a life-threatening condition in which placental trophoblastic cells abnormally invade the uterus, often up to the uterine serosa and, in extreme cases, tissues beyond the uterine wall. Currently, there is no clinical assay for the non-invasive detection of PAS, and only ultrasound and MRI can be used for its diagnosis. Considering the subjectivity of visual assessment, the detection of PAS necessitates a high degree of expertise and, in some instances, can lead to its misdiagnosis. In clinical practice, up to 50% of pregnancies with PAS remain undiagnosed until delivery, and it is associated with increased risk of morbidity/mortality. Although many studies have evaluated the potential of fetal biomarkers circulating in maternal blood, very few studies have evaluated the potential of circulating placental extracellular vesicles (EVs) and their miRNA contents for molecular detection of PAS. Thus, to purify placental EVs from maternal blood, we customized our robust ultra-sensitive immuno-purification assay, termed EV-CATCHER, with a monoclonal antibody targeting the membrane Placental Alkaline Phosphatase (PLAP) protein, which is unique to the placenta and present on the surface of placental EVs. Then, as a pilot evaluation, we compared the miRNA expression profiles of placental EVs purified from the maternal plasma of women diagnosed with placenta previa (controls, n = 16); placenta lying low in uterus but not invasive) to those of placental EVs purified from the plasma of women with placenta percreta (cases, n = 16), PAS with the highest level of invasiveness. Our analyses reveal that miRNA profiling of PLAP+ EVs purified from maternal plasma identified 40 differentially expressed miRNAs when comparing these two placental pathologies. Preliminary miRNA pathway enrichment and gene ontology analysis of the top 14 upregulated and top nine downregulated miRNAs in PLAP+ EVs, purified from the plasma of women diagnosed with placenta percreta versus those diagnosed with placenta previa, suggests a potential role in control of cellular invasion and motility that will require further investigation.
Full article
(This article belongs to the Special Issue Extracellular Vesicles in Reproduction 3.0)
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Open AccessArticle
p20BAP31 Induces Autophagy in Colorectal Cancer Cells by Promoting PERK-Mediated ER Stress
by
Xiaohan Jiang, Guoxun Li, Benzhi Zhu, Jiaying Yang, Shuyu Cui, Rui Jiang and Bing Wang
Int. J. Mol. Sci. 2024, 25(10), 5101; https://doi.org/10.3390/ijms25105101 - 07 May 2024
Abstract
B-cell receptor-associated protein 31 (BAP31) is an endoplasmic reticulum (ER) membrane protein involved in apoptosis and autophagy by communication with ER and mitochondria. BAP31 is cleaved by caspase-8 and generates a proapoptotic fragment, p20BAP31, which has shown to induce ER stress and apoptosis
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B-cell receptor-associated protein 31 (BAP31) is an endoplasmic reticulum (ER) membrane protein involved in apoptosis and autophagy by communication with ER and mitochondria. BAP31 is cleaved by caspase-8 and generates a proapoptotic fragment, p20BAP31, which has shown to induce ER stress and apoptosis through multiple pathways. In this study, we found that p20BAP31 significantly increased the agglomeration of LC3 puncta, suggesting the occurrence of autophagy. Therefore, it is meaningful to explore the mechanism of p20BAP31-induced autophagy, and further analyze the relationships among p20BAP31-induced autophagy, ER stress and apoptosis. The data showed that p20BAP31 induced autophagy by inhibition of the PI3K/AKT/mTOR signaling in colorectal cells. ER stress inhibitor 4-PBA and PERK siRNA alleviated p20BAP31-induced autophagy; in turn, autophagy inhibitors 3-MA and CQ did not affect p20BAP31-induced ER stress, suggesting that p20BAP31-induced ER stress is the upstream of autophagy. We also discovered that ROS inhibitor NAC inhibited p20BAP31-induced autophagy. Furthermore, inhibition of autophagy by CQ suppressed p20BAP31-induced apoptosis and ameliorated cell proliferation. Importantly, p20BAP31 markedly reduced the tumor size in vivo, and significantly enhanced the autophagy levels in the tumor tissues. Collectively, p20BAP31 initiates autophagy by inhibiting the PI3K/AKT/mTOR signaling and activating the PERK-mediated ROS accumulation, further promotes p20BAP31-induced apoptosis and ultimately results in cell death. This study comprehensively reveals the potential mechanism of p20BAP31-induced cell death, which may provide new strategies for antitumor therapy.
Full article
(This article belongs to the Section Molecular Oncology)
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Open AccessArticle
RNA-Seq Reveals That Multiple Pathways Are Involved in Tuber Expansion in Tiger Nuts (Cyperus esculentus L.)
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Guangshan Hou, Guojiang Wu, Huawu Jiang, Xue Bai and Yaping Chen
Int. J. Mol. Sci. 2024, 25(10), 5100; https://doi.org/10.3390/ijms25105100 - 07 May 2024
Abstract
The tiger nut (Cyperus esculentus L.) is a usable tuber and edible oil plant. The size of the tubers is a key trait that determines the yield and the mechanical harvesting of tiger nut tubers. However, little is known about the anatomical
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The tiger nut (Cyperus esculentus L.) is a usable tuber and edible oil plant. The size of the tubers is a key trait that determines the yield and the mechanical harvesting of tiger nut tubers. However, little is known about the anatomical and molecular mechanisms of tuber expansion in tiger nut plants. This study conducted anatomical and comprehensive transcriptomics analyses of tiger nut tubers at the following days after sowing: 40 d (S1); 50 d (S2); 60 d (S3); 70 d (S4); 90 d (S5); and 110 d (S6). The results showed that, at the initiation stage of a tiger nut tuber (S1), the primary thickening meristem (PTM) surrounded the periphery of the stele and was initially responsible for the proliferation of parenchyma cells of the cortex (before S1) and then the stele (S2–S3). The increase in cell size of the parenchyma cells occurred mainly from S1 to S3 in the cortex and from S3 to S4 in the stele. A total of 12,472 differentially expressed genes (DEGs) were expressed to a greater extent in the S1–S3 phase than in S4–S6 phase. DEGs related to tuber expansion were involved in cell wall modification, vesicle transport, cell membrane components, cell division, the regulation of plant hormone levels, signal transduction, and metabolism. DEGs involved in the biosynthesis and the signaling of indole-3-acetic acid (IAA) and jasmonic acid (JA) were expressed highly in S1–S3. The endogenous changes in IAA and JAs during tuber development showed that the highest concentrations were found at S1 and S1–S3, respectively. In addition, several DEGs were related to brassinosteroid (BR) signaling and the G-protein, MAPK, and ubiquitin–proteasome pathways, suggesting that these signaling pathways have roles in the tuber expansion of tiger nut. Finally, we come to the conclusion that the cortex development preceding stele development in tiger nut tubers. The auxin signaling pathway promotes the division of cortical cells, while the jasmonic acid pathway, brassinosteroid signaling, G-protein pathway, MAPK pathway, and ubiquitin protein pathway regulate cell division and the expansion of the tuber cortex and stele. This finding will facilitate searches for genes that influence tuber expansion and the regulatory networks in developing tubers.
Full article
(This article belongs to the Special Issue Formation, Regulation and Affecting Factors of Fruit Quality)
Open AccessCommunication
Convenient Preparation, Thermal Properties and X-ray Structure Determination of 2,3-Dihydro-5,6,7,8-tetranitro-1,4-benzodioxine (TNBD): A Promising High-Energy-Density Material
by
Jonas Šarlauskas
Int. J. Mol. Sci. 2024, 25(10), 5099; https://doi.org/10.3390/ijms25105099 - 07 May 2024
Abstract
2,3-dihydro-5,6,7,8-tetranitro-1,4-benzodioxine (TNBD), molecular formula =C8H4N4O10, is a completely nitrated aromatic ring 1,4-benzodioxane derivative. The convenient method of TNBD synthesis was developed (yield = 81%). The detailed structure of this compound was investigated by X-ray crystallography. The results of the thermal analysis (TG) obtained
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2,3-dihydro-5,6,7,8-tetranitro-1,4-benzodioxine (TNBD), molecular formula =C8H4N4O10, is a completely nitrated aromatic ring 1,4-benzodioxane derivative. The convenient method of TNBD synthesis was developed (yield = 81%). The detailed structure of this compound was investigated by X-ray crystallography. The results of the thermal analysis (TG) obtained with twice re-crystallized material revealed the onset at 240 °C (partial sublimation started) and melting at 286 °C. The investigated material degraded completely at 290–329 °C. The experimental density of 1.85 g/cm3 of TNBD was determined by X-ray crystallography. The spectral properties of TNBD (NMR, FT-IR and Raman) were explored. The detonation properties of TNBD calculated by the EXPLO 5 code were slightly superior in comparison to standard high-energy material—tetryl (detonation velocity of TNBD—7727 m/s; detonation pressure—278 kbar; and tetryl—7570 m/s and 226.4 kbar at 1.614 g/cm3, or 260 kbar at higher density at 1.71 g/cm3. The obtained preliminary results might suggest TNBD can be a potential thermostable high-energy and -density material (HEDM).
Full article
(This article belongs to the Special Issue Molecular Research on Energetic Materials)
Open AccessArticle
Assessment of Untargeted Metabolomics by Hydrophilic Interaction Liquid Chromatography−Mass Spectrometry to Define Breast Cancer Liquid Biopsy-Based Biomarkers in Plasma Samples
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Carmen González Olmedo, Leticia Díaz Beltrán, Verónica Madrid García, José Luis Palacios Ferrer, Alicia Cano Jiménez, Rocío Urbano Cubero, José Pérez del Palacio, Caridad Díaz, Francisca Vicente and Pedro Sánchez Rovira
Int. J. Mol. Sci. 2024, 25(10), 5098; https://doi.org/10.3390/ijms25105098 - 07 May 2024
Abstract
An early diagnosis of cancer is fundamental not only in regard to reducing its mortality rate but also in terms of counteracting the progression of the tumor in the initial stages. Breast cancer (BC) is the most common tumor pathology in women and
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An early diagnosis of cancer is fundamental not only in regard to reducing its mortality rate but also in terms of counteracting the progression of the tumor in the initial stages. Breast cancer (BC) is the most common tumor pathology in women and the second deathliest cancer worldwide, although its survival rate is increasing thanks to improvements in screening programs. However, the most common techniques to detect a breast tumor tend to be time-consuming, unspecific or invasive. Herein, the use of untargeted hydrophilic interaction liquid chromatography−mass spectrometry analysis appears as an analytical technique with potential use for the early detection of biomarkers in liquid biopsies from BC patients. In this research, plasma samples from 134 BC patients were compared with 136 from healthy controls (HC), and multivariate statistical analyses showed a clear separation between four BC phenotypes (LA, LB, HER2, and TN) and the HC group. As a result, we identified two candidate biomarkers that discriminated between the groups under study with a VIP > 1 and an AUC of 0.958. Thus, targeting the specific aberrant metabolic pathways in future studies may allow for better molecular stratification or early detection of the disease.
Full article
(This article belongs to the Special Issue New Diagnostic Tools and Biomarkers in Oncological Diseases 2.0)
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Open AccessArticle
Real-Time PCR Method as Diagnostic Tool for Detection of Periodontal Pathogens in Patients with Periodontitis
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Sendi Kuret, Nina Kalajzic, Matija Ruzdjak, Blaženka Grahovac, Marina Adriana Jezina Buselic, Sanda Sardelić, Anja Delic, Lana Susak and Davorka Sutlovic
Int. J. Mol. Sci. 2024, 25(10), 5097; https://doi.org/10.3390/ijms25105097 - 07 May 2024
Abstract
The most common type of periodontal disease is chronic periodontitis, an inflammatory condition caused by pathogenic bacteria in subgingival plaque. The aim of our study was the development of a real-time PCR test as a diagnostic tool for the detection and differentiation of
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The most common type of periodontal disease is chronic periodontitis, an inflammatory condition caused by pathogenic bacteria in subgingival plaque. The aim of our study was the development of a real-time PCR test as a diagnostic tool for the detection and differentiation of five periodontopathogenic bacteria, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia, and Treponema denticola, in patients with periodontitis. We compared the results of our in-house method with the micro-IDent® semiquantitative commercially available test based on the PCR hybridization method. DNA was isolated from subgingival plaque samples taken from 50 patients and then analyzed by both methods. Comparing the results of the two methods, they show a specificity of 100% for all bacteria. The sensitivity for A. actinomycetemcomitans was 97.5%, for P. gingivalis 96.88%, and for P. intermedia 95.24%. The sensitivity for Tannerella forsythia and T. denticola was 100%. The Spearman correlation factor of two different measurements was 0.976 for A. actinomycetemcomitans, 0.967 for P. gingivalis, 0.949 for P. intermedia, 0.966 for Tannerella forsythia, and 0.917 for T. denticola. In conclusion, the in-house real-time PCR method developed in our laboratory can provide information about relative amount of five bacterial species present in subgingival plaque in patients with periodontitis. It is likely that such a test could be used in dental diagnostics in assessing the efficacy of any treatment to reduce the bacterial burden.
Full article
(This article belongs to the Special Issue Oral and Dental Infectious Diseases: Molecular Pathology, Diagnosis and Therapy)
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Open AccessArticle
DNA Methylation Analysis of Growth Differences between Upright and Inverted Cuttings of Populus yunnanensis
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Haiyang Guo, Tiansu Guo, Hailin Li, Shaojie Ma, Xiaolin Zhang, Chengzhong He and Dan Zong
Int. J. Mol. Sci. 2024, 25(10), 5096; https://doi.org/10.3390/ijms25105096 - 07 May 2024
Abstract
DNA methylation is an important mechanism for epigenetic modifications that have been shown to be associated with responses to plant development. Previous studies found that inverted Populus yunnanensis cuttings were still viable and could develop into complete plants. However, the growth status of
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DNA methylation is an important mechanism for epigenetic modifications that have been shown to be associated with responses to plant development. Previous studies found that inverted Populus yunnanensis cuttings were still viable and could develop into complete plants. However, the growth status of inverted cuttings was weaker than that of upright cuttings, and the sprouting time of inverted cuttings was later than that of upright cuttings. There is currently no research on DNA methylation patterns in inverted cuttings of Populus yunnanensis. In this study, we detected genome-wide methylation patterns of stem tips of Populus yunnanensis at the early growth stage and the rapid growth stage by Oxford Nanopore Technologies (ONT) methylation sequencing. We found that the methylation levels of CpG, CHG, CHH, and 6mA were 41.34%, 33.79%, 17.27%, and 12.90%, respectively, in the genome of inverted poplar cuttings, while the methylation levels of the four methylation types were higher in the genome of upright poplar cuttings than in inverted cuttings, 41.90%, 34.57%, 18.09%, and 14.11%, suggesting important roles for DNA methylation in poplar cells. In all comparison groups, CpG-type methylation genes in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were annotated to pathways associated with carbon metabolism, ribosome biogenesis in eukaryotes, glycolysis/gluconeogenesis, pyruvate metabolism, and mRNA detection pathways, suggesting that different biological processes are activated in upright and inverted cuttings. The results show that methylation genes are commonly present in the poplar genome, but only a few of them are involved in the regulation of expression in the growth and development of inverted cuttings. From this, we screened the DET2 gene for significant differences in methylation levels in upright or inverted cuttings. The DET2 gene is a key gene in the Brassinolide (BRs) synthesis pathway, and BRs have an important influence on the growth and development process of plants. These results provide important clues for studying DNA methylation patterns in P. yunnanensis.
Full article
(This article belongs to the Section Molecular Plant Sciences)
Open AccessCase Report
Chronological Changes in the Histology of Infection-Related Glomerulonephritis in Renal Allograft: A Case Report
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Kenta Tominaga, Takashi Oda, Sachiko Iwama, Tadasu Kojima, Osamu Konno, Muneharu Yamada, Iwao Nakabayashi and Hitoshi Iwamoto
Int. J. Mol. Sci. 2024, 25(10), 5095; https://doi.org/10.3390/ijms25105095 - 07 May 2024
Abstract
We report the histological changes over time for a patient with infection-related glomerulonephritis (IRGN) that developed in a transplanted kidney. A 47-year-old man had undergone renal transplantation 3 years ago for end-stage kidney disease (ESKD). After several episodes of acute rejection, the patient
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We report the histological changes over time for a patient with infection-related glomerulonephritis (IRGN) that developed in a transplanted kidney. A 47-year-old man had undergone renal transplantation 3 years ago for end-stage kidney disease (ESKD). After several episodes of acute rejection, the patient was in a stable CKD condition. The abrupt development of severe microscopic hematuria and renal dysfunction was observed approximately 2 weeks after the onset of a phlegmon in his right leg. An allograft biopsy showed prominent glomerular endocapillary proliferation on light microscopy, granular C3 deposition on immunofluorescent microscopy, and subepithelial electron-dense deposits on electron microscopy, suggesting IRGN accompanied by moderate interstitial fibrosis and tubular atrophy (IFTA). Positive glomerular staining for nephritis-associated plasmin receptor (NAPlr) and plasmin activity, which are biomarkers of bacterial IRGN, supported the diagnosis. Although the infection was completely cured with antibiotic therapy, renal dysfunction persisted. A re-biopsy of the allograft 2 months later revealed resolution of the glomerular endocapillary proliferation and negative staining for NAPlr/plasmin activity, with worsening IFTA. We showed, for the first time, the chronological changes in infiltrating cells and histological markers of IRGN in transplanted kidneys. Glomerular changes, including NAPlr/plasmin activity staining, almost disappeared after the cessation of infection, while interstitial changes continuously progressed, contributing to ESKD progression.
Full article
(This article belongs to the Section Molecular Immunology)
Open AccessArticle
Ionization Detail Parameters for DNA Damage Evaluation in Charged Particle Radiotherapy: Simulation Study Based on Cell Survival Database
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Monika Mietelska, Marcin Pietrzak, Aleksandr Bancer, Antoni Ruciński, Zygmunt Szefliński and Beata Brzozowska
Int. J. Mol. Sci. 2024, 25(10), 5094; https://doi.org/10.3390/ijms25105094 - 07 May 2024
Abstract
Details of excitation and ionization acts hide a description of the biological effects of charged particle traversal through living tissue. Nanodosimetry enables the introduction of novel quantities that characterize and quantify the particle track structure while also serving as a foundation for assessing
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Details of excitation and ionization acts hide a description of the biological effects of charged particle traversal through living tissue. Nanodosimetry enables the introduction of novel quantities that characterize and quantify the particle track structure while also serving as a foundation for assessing biological effects based on this quantification. This presents an opportunity to enhance the planning of charged particle radiotherapy by taking into account the ionization detail. This work uses Monte Carlo simulations with Geant4-DNA code for a wide variety of charged particles and their radiation qualities to analyze the distribution of ionization cluster sizes within nanometer-scale volumes, similar to DNA diameter. By correlating these results with biological parameters extracted from the PIDE database for the V79 cell line, a novel parameter based on ionization details is proposed for the evaluation of radiation quality in terms of biological consequences, i.e., radiobiological cross section for inactivation. By incorporating the probability p of sub-lethal damage caused by a single ionization, we address limitations associated with the usually proposed nanodosimetric parameter for characterizing the biological effects of radiation. We show that the new parameter correlates well with radiobiological data and can be used to predict biological outcomes.
Full article
(This article belongs to the Section Molecular Biology)
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Open AccessReview
Ca2+-Dependent Cl− Channels in Vascular Tone Regulation during Aging
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Miriam Petrova, Monika Lassanova, Jana Tisonova and Silvia Liskova
Int. J. Mol. Sci. 2024, 25(10), 5093; https://doi.org/10.3390/ijms25105093 - 07 May 2024
Abstract
Identifying alterations caused by aging could be an important tool for improving the diagnosis of cardiovascular diseases. Changes in vascular tone regulation involve various mechanisms, like NO synthase activity, activity of the sympathetic nervous system, production of prostaglandin, endothelium-dependent relaxing, and contracting factors,
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Identifying alterations caused by aging could be an important tool for improving the diagnosis of cardiovascular diseases. Changes in vascular tone regulation involve various mechanisms, like NO synthase activity, activity of the sympathetic nervous system, production of prostaglandin, endothelium-dependent relaxing, and contracting factors, etc. Surprisingly, Ca2+-dependent Cl− channels (CaCCs) are involved in all alterations of the vascular tone regulation mentioned above. Furthermore, we discuss these mechanisms in the context of ontogenetic development and aging. The molecular and electrophysiological mechanisms of CaCCs activation on the cell membrane of the vascular smooth muscle cells (VSMC) and endothelium are explained, as well as the age-dependent changes that imply the activation or inhibition of CaCCs. In conclusion, due to the diverse intracellular concentration of chloride in VSMC and endothelial cells, the activation of CaCCs depends, in part, on intracellular Ca2+ concentration, and, in part, on voltage, leading to fine adjustments of vascular tone. The activation of CaCCs declines during ontogenetic development and aging. This decline in the activation of CaCCs involves a decrease in protein level, the impairment of Ca2+ influx, and probably other alterations in vascular tone regulation.
Full article
(This article belongs to the Special Issue Aging in Cardiovascular Diseases)
Open AccessArticle
Comparative Transcriptome Analysis Reveals the Protective Role of Melatonin during Salt Stress by Regulating the Photosynthesis and Ascorbic Acid Metabolism Pathways in Brassica campestris
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Sayyed Hamad Ahmad Shah, Haibin Wang, Huanhuan Xu, Zhanghong Yu, Xilin Hou and Ying Li
Int. J. Mol. Sci. 2024, 25(10), 5092; https://doi.org/10.3390/ijms25105092 - 07 May 2024
Abstract
Salinity stress is a type of abiotic stress which negatively affects the signaling pathways and cellular compartments of plants. Melatonin (MT) has been found to be a bioactive compound that can mitigate these adverse effects, which makes it necessary to understand the function
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Salinity stress is a type of abiotic stress which negatively affects the signaling pathways and cellular compartments of plants. Melatonin (MT) has been found to be a bioactive compound that can mitigate these adverse effects, which makes it necessary to understand the function of MT and its role in salt stress. During this study, plants were treated exogenously with 100 µM of MT for 7 days and subjected to 200 mM of salt stress, and samples were collected after 1 and 7 days for different indicators and transcriptome analysis. The results showed that salt reduced chlorophyll contents and damaged the chloroplast structure, which was confirmed by the downregulation of key genes involved in the photosynthesis pathway after transcriptome analysis and qRT-PCR confirmation. Meanwhile, MT increased the chlorophyll contents, reduced the electrolyte leakage, and protected the chloroplast structure during salt stress by upregulating several photosynthesis pathway genes. MT also decreased the H2O2 level and increased the ascorbic acid contents and APX activity by upregulating genes involved in the ascorbic acid pathway during salt stress, as confirmed by the transcriptome and qRT-PCR analyses. Transcriptome profiling also showed that 321 and 441 DEGs were expressed after 1 and 7 days of treatment, respectively. The KEGG enrichment analysis showed that 76 DEGs were involved in the photosynthesis pathway, while 35 DEGs were involved in the ascorbic acid metabolism pathway, respectively. These results suggest that the exogenous application of MT in plants provides important insight into understanding MT-induced stress-responsive mechanisms and protecting Brassica campestris against salt stress by regulating the photosynthesis and ascorbic acid pathway genes.
Full article
(This article belongs to the Section Molecular Plant Sciences)
Open AccessArticle
Synthesis, In Silico Study, and In Vitro Antifungal Activity of New 5-(1,3-Diphenyl-1H-Pyrazol-4-yl)-4-Tosyl-4,5-Dihydrooxazoles
by
Neively Tlapale-Lara, Julio López, Elizabeth Gómez, Lourdes Villa-Tanaca, Edson Barrera, Carlos H. Escalante, Joaquín Tamariz, Francisco Delgado, Dulce Andrade-Pavón and Omar Gómez-García
Int. J. Mol. Sci. 2024, 25(10), 5091; https://doi.org/10.3390/ijms25105091 - 07 May 2024
Abstract
The increase in multi-drug resistant Candida strains has caused a sharp rise in life-threatening fungal infections in immunosuppressed patients, including those with SARS-CoV-2. Novel antifungal drugs are needed to combat multi-drug-resistant yeasts. This study aimed to synthesize a new series of 2-oxazolines and
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The increase in multi-drug resistant Candida strains has caused a sharp rise in life-threatening fungal infections in immunosuppressed patients, including those with SARS-CoV-2. Novel antifungal drugs are needed to combat multi-drug-resistant yeasts. This study aimed to synthesize a new series of 2-oxazolines and evaluate the ligands in vitro for the inhibition of six Candida species and in silico for affinity to the CYP51 enzymes (obtained with molecular modeling and protein homology) of the same species. The 5-(1,3-diphenyl-1H-pyrazol-4-yl)-4-tosyl-4,5-dihydrooxazoles 6a-j were synthesized using the Van Leusen reaction between 1,3-diphenyl-4-formylpyrazoles 4a-j and TosMIC 5 in the presence of K2CO3 or KOH without heating, resulting in short reaction times, high compound purity, and high yields. The docking studies revealed good affinity for the active site of the CYP51 enzymes of the Candida species in the following order: 6a-j > 4a-j > fluconazole (the reference drug). The in vitro testing of the compounds against the Candida species showed lower MIC values for 6a-j than 4a-j, and for 4a-j than fluconazole, thus correlating well with the in silico findings. According to growth rescue assays, 6a-j and 4a-j (like fluconazole) inhibit ergosterol synthesis. The in silico toxicity assessment evidenced the safety of compounds 6a-j, which merit further research as possible antifungal drugs.
Full article
(This article belongs to the Special Issue Antifungal Drug Design, Synthesis and Molecular Mechanisms)
Open AccessArticle
Restoration of Lactobacillus johnsonii and Enterococcus faecalis Caused the Elimination of Tritrichomonas sp. in a Model of Antibiotic-Induced Dysbiosis
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Yulia Makusheva, Elena Goncharova, Victoria Bets, Anastasya Korel, Elena Arzhanova and Ekaterina Litvinova
Int. J. Mol. Sci. 2024, 25(10), 5090; https://doi.org/10.3390/ijms25105090 - 07 May 2024
Abstract
Inflammatory bowel disease (IBD) is a multifactorial disease involving the interaction of the gut microbiota, genes, host immunity, and environmental factors. Dysbiosis in IBD is associated with pathobiont proliferation, so targeted antibiotic therapy is a rational strategy. When restoring the microbiota with probiotics,
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Inflammatory bowel disease (IBD) is a multifactorial disease involving the interaction of the gut microbiota, genes, host immunity, and environmental factors. Dysbiosis in IBD is associated with pathobiont proliferation, so targeted antibiotic therapy is a rational strategy. When restoring the microbiota with probiotics, it is necessary to take into account the mutual influence of co-cultivated microorganisms, as the microbiota is a dynamic community of species that mediates homeostasis and physiological processes in the intestine. The aim of our study was to investigate the recovery efficacy of two potential probiotic bacteria, L. johnsonii and E. faecalis, in Muc2−/− mice with impaired mucosal layer. Two approaches were used to determine the efficacy of probiotic supplementation in mice with dysbiosis caused by mucin-2 deficiency: bacterial seeding on selective media and real-time PCR analysis. The recovery time and the type of probiotic bacteria relocated affected only the number of E. faecalis. A significant positive correlation was found between colony-forming unit (CFU) and the amount of E. faecalis DNA in the group that was replanted with probiotic E. faecalis. As for L. johnsonii, it could be restored to its original level even without any additional bacteria supplementation after two weeks. Interestingly, the treatment of mice with L. johnsonii caused a decrease in the amount of E. faecalis. Furthermore, either L. johnsonii or E. faecalis treatment eliminated protozoan overgrowth caused by antibiotic administration.
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(This article belongs to the Special Issue Molecular Diagnosis and Treatment of Inflammatory Bowel Disease)
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Nonribosomal Peptide Synthetase Specific Genome Amplification Using Rolling Circle Amplification for Targeted Gene Sequencing
by
Yoshiko Okamura, Masahiro Suemitsu, Takato Ishikawa and Hirokazu Takahashi
Int. J. Mol. Sci. 2024, 25(10), 5089; https://doi.org/10.3390/ijms25105089 - 07 May 2024
Abstract
Next-generation sequencing has transformed the acquisition of vast amounts of genomic information, including the rapid identification of target gene sequences in metagenomic databases. However, dominant species can sometimes hinder the detection of rare bacterial species. Therefore, a highly sensitive amplification technique that can
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Next-generation sequencing has transformed the acquisition of vast amounts of genomic information, including the rapid identification of target gene sequences in metagenomic databases. However, dominant species can sometimes hinder the detection of rare bacterial species. Therefore, a highly sensitive amplification technique that can selectively amplify bacterial genomes containing target genes of interest was developed in this study. The rolling circle amplification (RCA) method can initiate amplification from a single locus using a specific single primer to amplify a specific whole genome. A mixed cell suspension was prepared using Pseudomonas fluorescens ATCC17400 (targeting nonribosomal peptide synthetase [NRPS]) and Escherichia coli (non-target), and a specific primer designed for the NRPS was used for the RCA reaction. The resulting RCA product (RCP) amplified only the Pseudomonas genome. The NRPS was successfully amplified using RCP as a template from even five cells, indicating that the single-priming RCA technique can specifically enrich the target genome using gene-specific primers. Ultimately, this specific genome RCA technique was applied to metagenomes extracted from sponge-associated bacteria, and NRPS sequences were successfully obtained from an unknown sponge-associated bacterium. Therefore, this method could be effective for accessing species-specific sequences of NRPS in unknown bacteria, including viable but non-culturable bacteria.
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(This article belongs to the Section Molecular Genetics and Genomics)
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Design and Synthesis of Biomedical Polymer Materials
by
Jie Chen
Int. J. Mol. Sci. 2024, 25(10), 5088; https://doi.org/10.3390/ijms25105088 - 07 May 2024
Abstract
Due to their biocompatibility and non-toxic nature, biomedical polymer materials have found widespread applications and significantly propelled the progress of the biomedical field [...]
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(This article belongs to the Special Issue Design and Synthesis of Biomedical Polymer Materials)
Open AccessArticle
MiR-148a-3p/SIRT7 Axis Relieves Inflammatory-Induced Endothelial Dysfunction
by
Camilla Anastasio, Isabella Donisi, Antonino Colloca, Nunzia D’Onofrio and Maria Luisa Balestrieri
Int. J. Mol. Sci. 2024, 25(10), 5087; https://doi.org/10.3390/ijms25105087 - 07 May 2024
Abstract
In endothelial cells, miR-148a-3p is involved in several pathological pathways, including chronic inflammatory conditions. However, the molecular mechanism of miR-148a-3p in endothelial inflammatory states is, to date, not fully elucidated. To this end, we investigated the involvement of miR-148a-3p in mitochondrial dysfunction and
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In endothelial cells, miR-148a-3p is involved in several pathological pathways, including chronic inflammatory conditions. However, the molecular mechanism of miR-148a-3p in endothelial inflammatory states is, to date, not fully elucidated. To this end, we investigated the involvement of miR-148a-3p in mitochondrial dysfunction and cell death pathways in human aortic endothelial cells (teloHAECs) treated with interleukin-6 (IL-6), a major driver of vascular dysfunction. The results showed that during IL6-activated inflammatory pathways, including increased protein levels of sirtuin 7 (SIRT7) (p < 0.01), mitochondrial stress (p < 0.001), and apoptosis (p < 0.01), a decreased expression of miR-148a-3p was observed (p < 0.01). The employment of a miR-148a mimic counteracted the IL-6-induced cytokine release (p < 0.01) and apoptotic cell death (p < 0.01), and ameliorated mitochondria redox homeostasis and respiration (p < 0.01). The targeted relationship between miR-148a-3p and SIRT7 was predicted by a bioinformatics database analysis and validated via the dual-luciferase reporter assay. Mechanistically, miR-148a-3p targets the 3′ untranslated regions of SIRT7 mRNA, downregulating its expression (p < 0.01). Herein, these in vitro results support the role of the miR-148a-3p/SIRT7 axis in counteracting mitochondrial damage and apoptosis during endothelial inflammation, unveiling a novel target for future strategies to prevent endothelial dysfunction.
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(This article belongs to the Special Issue Endothelial Dysfunction: Molecular Mechanisms and Therapeutic Strategies)
Open AccessArticle
Upregulation of Hepatic Glutathione S-Transferase Alpha 1 Ameliorates Metabolic Dysfunction-Associated Steatosis by Degrading Fatty Acid Binding Protein 1
by
Jing Jiang, Hu Li, Mei Tang, Lei Lei, Hong-Ying Li, Biao Dong, Jian-Rui Li, Xue-Kai Wang, Han Sun, Jia-Yu Li, Jing-Chen Xu, Yue Gong, Jian-Dong Jiang and Zong-Gen Peng
Int. J. Mol. Sci. 2024, 25(10), 5086; https://doi.org/10.3390/ijms25105086 - 07 May 2024
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common metabolic disease of the liver, characterized by hepatic steatosis in more than 5% of hepatocytes. However, despite the recent approval of the first drug, resmetirom, for the management of metabolic dysfunction-associated steatohepatitis, decades
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Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common metabolic disease of the liver, characterized by hepatic steatosis in more than 5% of hepatocytes. However, despite the recent approval of the first drug, resmetirom, for the management of metabolic dysfunction-associated steatohepatitis, decades of target exploration and hundreds of clinical trials have failed, highlighting the urgent need to find new druggable targets for the discovery of innovative drug candidates against MASLD. Here, we found that glutathione S-transferase alpha 1 (GSTA1) expression was negatively associated with lipid droplet accumulation in vitro and in vivo. Overexpression of GSTA1 significantly attenuated oleic acid-induced steatosis in hepatocytes or high-fat diet-induced steatosis in the mouse liver. The hepatoprotective and anti-inflammatory drug bicyclol also attenuated steatosis by upregulating GSTA1 expression. A detailed mechanism showed that GSTA1 directly interacts with fatty acid binding protein 1 (FABP1) and facilitates the degradation of FABP1, thereby inhibiting intracellular triglyceride synthesis by impeding the uptake and transportation of free fatty acids. Conclusion: GSTA1 may be a good target for the discovery of innovative drug candidates as GSTA1 stabilizers or enhancers against MASLD.
Full article
(This article belongs to the Special Issue Exploring the Interplay among NAFLD, Insulin Resistance, and Metabolic Disorders: Mechanisms, Diagnosis, and Therapeutic Strategies)
Open AccessReview
Chronic Stress-Induced Neuroinflammation: Relevance of Rodent Models to Human Disease
by
Abigail G. White, Elias Elias, Andrea Orozco, Shivon A. Robinson and Melissa T. Manners
Int. J. Mol. Sci. 2024, 25(10), 5085; https://doi.org/10.3390/ijms25105085 - 07 May 2024
Abstract
The brain is the central organ of adaptation to stress because it perceives and determines threats that induce behavioral, physiological, and molecular responses. In humans, chronic stress manifests as an enduring consistent feeling of pressure and being overwhelmed for an extended duration. This
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The brain is the central organ of adaptation to stress because it perceives and determines threats that induce behavioral, physiological, and molecular responses. In humans, chronic stress manifests as an enduring consistent feeling of pressure and being overwhelmed for an extended duration. This can result in a persistent proinflammatory response in the peripheral and central nervous system (CNS), resulting in cellular, physiological, and behavioral effects. Compounding stressors may increase the risk of chronic-stress-induced inflammation, which can yield serious health consequences, including mental health disorders. This review summarizes the current knowledge surrounding the neuroinflammatory response in rodent models of chronic stress—a relationship that is continually being defined. Many studies investigating the effects of chronic stress on neuroinflammation in rodent models have identified significant changes in inflammatory modulators, including nuclear factor-κB (NF-κB) and toll-like receptors (TLRs), and cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6. This suggests that these are key inflammatory factors in the chronic stress response, which may contribute to the establishment of anxiety and depression-like symptoms. The behavioral and neurological effects of modulating inflammatory factors through gene knockdown (KD) and knockout (KO), and conventional and alternative medicine approaches, are discussed.
Full article
(This article belongs to the Special Issue Depression: From Molecular Basis to Therapy)
Open AccessArticle
A New Approach in Lipase-Octyl-Agarose Biocatalysis of 2-Arylpropionic Acid Derivatives
by
Joanna Siódmiak, Jacek Dulęba, Natalia Kocot, Rafał Mastalerz, Gudmundur G. Haraldsson, Michał Piotr Marszałł and Tomasz Siódmiak
Int. J. Mol. Sci. 2024, 25(10), 5084; https://doi.org/10.3390/ijms25105084 - 07 May 2024
Abstract
The use of lipase immobilized on an octyl-agarose support to obtain the optically pure enantiomers of chiral drugs in reactions carried out in organic solvents is a great challenge for chemical and pharmaceutical sciences. Therefore, it is extremely important to develop optimal procedures
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The use of lipase immobilized on an octyl-agarose support to obtain the optically pure enantiomers of chiral drugs in reactions carried out in organic solvents is a great challenge for chemical and pharmaceutical sciences. Therefore, it is extremely important to develop optimal procedures to achieve a high enantioselectivity of the biocatalysts in the organic medium. Our paper describes a new approach to biocatalysis performed in an organic solvent with the use of CALB-octyl-agarose support including the application of a polypropylene reactor, an appropriate buffer for immobilization (Tris base—pH 9, 100 mM), a drying step, and then the storage of immobilized lipases in a climatic chamber or a refrigerator. An immobilized lipase B from Candida antarctica (CALB) was used in the kinetic resolution of (R,S)-flurbiprofen by enantioselective esterification with methanol, reaching a high enantiomeric excess (eep = 89.6% ± 2.0%). As part of the immobilization optimization, the influence of different buffers was investigated. The effect of the reactor material and the reaction medium on the lipase activity was also studied. Moreover, the stability of the immobilized lipases: lipase from Candida rugosa (CRL) and CALB during storage in various temperature and humidity conditions (climatic chamber and refrigerator) was tested. The application of the immobilized CALB in a polypropylene reactor allowed for receiving over 9-fold higher conversion values compared to the results achieved when conducting the reaction in a glass reactor, as well as approximately 30-fold higher conversion values in comparison with free lipase. The good stability of the CALB-octyl-agarose support was demonstrated. After 7 days of storage in a climatic chamber or refrigerator (with protection from humidity) approximately 60% higher conversion values were obtained compared to the results observed for the immobilized form that had not been stored. The new approach involving the application of the CALB-octyl-agarose support for reactions performed in organic solvents indicates a significant role of the polymer reactor material being used in achieving high catalytic activity.
Full article
(This article belongs to the Special Issue Developments and Advances in Biocatalysis of Chiral Drugs)
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