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
Unraveling Divergent Transcriptomic Profiles: A Comparative Single-Cell RNA Sequencing Study of Epithelium, Gingiva, and Periodontal Ligament Tissues
Int. J. Mol. Sci. 2024, 25(11), 5617; https://doi.org/10.3390/ijms25115617 (registering DOI) - 22 May 2024
Abstract
The periodontium comprising periodontal ligament (PDL), gingiva, and epithelium play crucial roles in maintaining tooth integrity and function. Understanding tissue cellular composition and gene expression is crucial for illuminating periodontal pathophysiology. This study aimed to identify tissue-specific markers via scRNA-Seq. Primary human PDL,
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The periodontium comprising periodontal ligament (PDL), gingiva, and epithelium play crucial roles in maintaining tooth integrity and function. Understanding tissue cellular composition and gene expression is crucial for illuminating periodontal pathophysiology. This study aimed to identify tissue-specific markers via scRNA-Seq. Primary human PDL, gingiva, and epithelium tissues (n = 7) were subjected to cell hashing and sorting. scRNA-Seq library preparation using 10× Genomics protocol and Illumina sequencing was conducted. The analysis was performed using Cellranger (v3.1.0), with downstream analysis via R packages Seurat (v5.0.1) and SCORPIUS (v1.0.9). Investigations identified eight distinct cellular clusters, revealing the ubiquitous presence of epithelial and gingival cells. PDL cells evolved in two clusters with numerical superiority. The other clusters showed varied predominance regarding gingival and epithelial cells or an equitable distribution of both. The cluster harboring most cells mainly consisted of PDL cells and was present in all donors. Some of the other clusters were also tissue-inherent, while the presence of others was environmentally influenced, revealing variability across donors. Two clusters exhibited genetic profiles associated with tissue development and cellular integrity, respectively, while all other clusters were distinguished by genes characteristic of immune responses. Developmental trajectory analysis uncovered that PDL cells may develop after epithelial and gingival cells, suggesting the inherent PDL cell-dominated cluster as a final developmental stage. This single-cell RNA sequencing study delineates the hierarchical organization of periodontal tissue development, identifies tissue-specific markers, and reveals the influence of environmental factors on cellular composition, advancing our understanding of periodontal biology and offering potential insights for therapeutic interventions.
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(This article belongs to the Special Issue Chemoinformatics and Bioinformatics Tools in Structure-Activity Modelling in Molecular Sciences 2.0)
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Open AccessArticle
Rabies Virus Infection Causes Pyroptosis of Neuronal Cells
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Dongling Yu, Rong Jin, Jundan Liu, Chuanliang Zhang, Chenxing Duan, Xi Luo, Wenhao Yang, Cheng Liu, Jingjing Liang, Xiaoning Li and Tingrong Luo
Int. J. Mol. Sci. 2024, 25(11), 5616; https://doi.org/10.3390/ijms25115616 (registering DOI) - 22 May 2024
Abstract
Rabies virus (RABV) is a neurotropic virus that causes fatal neurological disease, raising serious public health issues and attracting extensive attention in society. To elucidate the molecular mechanism of RABV-induced neuronal damage, we used hematoxylin–eosin staining, transmission electron microscopy, transcriptomics analysis, and immune
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Rabies virus (RABV) is a neurotropic virus that causes fatal neurological disease, raising serious public health issues and attracting extensive attention in society. To elucidate the molecular mechanism of RABV-induced neuronal damage, we used hematoxylin–eosin staining, transmission electron microscopy, transcriptomics analysis, and immune response factor testing to investigate RABV-infected neurons. We successfully isolated the neurons from murine brains. The specificity of the isolated neurons was identified by a monoclonal antibody, and the viability of the neurons was 83.53–95.0%. We confirmed that RABV infection induced serious damage to the neurons according to histochemistry and transmission electron microscope (TEM) scanning. In addition, the transcriptomics analysis suggested that multiple genes related to the pyroptosis pathway were significantly upregulated, including gasdermin D (Gsdmd), Nlrp3, caspase-1, and IL-1β, as well as the chemokine genes Ccl2, Ccl3, Ccl4, Ccl5, Ccl7, Ccl12, and Cxcl10. We next verified this finding in the brains of mice infected with the rRC-HL, GX074, and challenge virus standard strain-24 (CVS-24) strains of RABV. Importantly, we found that the expression level of the Gsdmd protein was significantly upregulated in the neurons infected with different RABV strains and ranged from 691.1 to 5764.96 pg/mL, while the basal level of mock-infected neurons was less than 100 pg/mL. Taken together, our findings suggest that Gsdmd-induced pyroptosis is involved in the neuron damage caused by RABV infection.
Full article
(This article belongs to the Special Issue Molecular Biology of Host and Pathogen Interactions 2.0)
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Open AccessArticle
Multi-Omics Analysis of a Chromosome Segment Substitution Line Reveals a New Regulation Network for Soybean Seed Storage Profile
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Cholnam Jong, Zhenhai Yu, Yu Zhang, Kyongho Choe, Songrok Uh, Kibong Kim, Chol Jong, Jinmyong Cha, Myongguk Kim, Yunchol Kim, Xue Han, Mingliang Yang, Chang Xu, Limin Hu, Qingshan Chen, Chunyan Liu and Zhaoming Qi
Int. J. Mol. Sci. 2024, 25(11), 5614; https://doi.org/10.3390/ijms25115614 (registering DOI) - 21 May 2024
Abstract
Soybean, a major source of oil and protein, has seen an annual increase in consumption when used in soybean-derived products and the broadening of its cultivation range. The demand for soybean necessitates a better understanding of the regulatory networks driving storage protein accumulation
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Soybean, a major source of oil and protein, has seen an annual increase in consumption when used in soybean-derived products and the broadening of its cultivation range. The demand for soybean necessitates a better understanding of the regulatory networks driving storage protein accumulation and oil biosynthesis to broaden its positive impact on human health. In this study, we selected a chromosome segment substitution line (CSSL) with high protein and low oil contents to investigate the underlying effect of donor introgression on seed storage through multi-omics analysis. In total, 1479 differentially expressed genes (DEGs), 82 differentially expressed proteins (DEPs), and 34 differentially expressed metabolites (DEMs) were identified in the CSSL compared to the recurrent parent. Based on Gene Ontology (GO) term analysis and the Kyoto Encyclopedia of Genes and Genomes enrichment (KEGG), integrated analysis indicated that 31 DEGs, 24 DEPs, and 13 DEMs were related to seed storage functionality. Integrated analysis further showed a significant decrease in the contents of the seed storage lipids LysoPG 16:0 and LysoPC 18:4 as well as an increase in the contents of organic acids such as L-malic acid. Taken together, these results offer new insights into the molecular mechanisms of seed storage and provide guidance for the molecular breeding of new favorable soybean varieties.
Full article
(This article belongs to the Special Issue Genetics and Novel Techniques for Soybean Pivotal Characters)
Open AccessArticle
Minimal Change Disease: Pathogenetic Insights from Glomerular Proteomics
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Andrada Alina Bărar, Ioana-Ecaterina Pralea, Yuriy Maslyennikov, Raluca Munteanu, Ioana Berindan-Neagoe, Radu Pîrlog, Ioana Rusu, Andreea Nuțu, Crina Claudia Rusu, Diana Tania Moldovan, Alina Ramona Potra, Dacian Tirinescu, Maria Ticala, Florin Ioan Elec, Cristina Adela Iuga and Ina Maria Kacso
Int. J. Mol. Sci. 2024, 25(11), 5613; https://doi.org/10.3390/ijms25115613 (registering DOI) - 21 May 2024
Abstract
The mechanism underlying podocyte dysfunction in minimal change disease (MCD) remains unknown. This study aimed to shed light on the potential pathophysiology of MCD using glomerular proteomic analysis. Shotgun proteomics using label-free quantitative mass spectrometry was performed on formalin-fixed, paraffin-embedded (FFPE) renal biopsies
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The mechanism underlying podocyte dysfunction in minimal change disease (MCD) remains unknown. This study aimed to shed light on the potential pathophysiology of MCD using glomerular proteomic analysis. Shotgun proteomics using label-free quantitative mass spectrometry was performed on formalin-fixed, paraffin-embedded (FFPE) renal biopsies from two groups of samples: control (CTR) and MCD. Glomeruli were excised from FFPE renal biopsies using laser capture microdissection (LCM), and a single-pot solid-phase-enhanced sample preparation (SP3) digestion method was used to improve yield and protein identifications. Principal component analysis (PCA) revealed a distinct separation between the CTR and MCD groups. Forty-eight proteins with different abundance between the two groups (p-value ≤ 0.05 and |FC| ≥ 1.5) were identified. These may represent differences in podocyte structure, as well as changes in endothelial or mesangial cells and extracellular matrix, and some were indeed found in several of these structures. However, most differentially expressed proteins were linked to the podocyte cytoskeleton and its dynamics. Some of these proteins are known to be involved in focal adhesion (NID1 and ITGA3) or slit diaphragm signaling (ANXA2, TJP1 and MYO1C), while others are structural components of the actin and microtubule cytoskeleton of podocytes (ACTR3 and NES). This study suggests the potential of mass spectrometry-based shotgun proteomic analysis with LCM glomeruli to yield valuable insights into the pathogenesis of podocytopathies like MCD. The most significantly dysregulated proteins in MCD could be attributable to cytoskeleton dysfunction or may be a compensatory response to cytoskeleton malfunction caused by various triggers.
Full article
(This article belongs to the Special Issue New Insights into Kidney Diseases)
Open AccessArticle
A Novel Minimally Invasive Surgically Induced Skeletal Muscle Injury Model in Sheep
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Laura Vidal, Ingrid Vila, Vanesa Venegas, Anabel Sacristán, Paola Contreras-Muñoz, Maria Lopez-Garzon, Carles Giné, Gil Rodas and Mario Marotta
Int. J. Mol. Sci. 2024, 25(11), 5612; https://doi.org/10.3390/ijms25115612 (registering DOI) - 21 May 2024
Abstract
Sports-related muscle injuries account for 10–55% of all injuries, which is a growing concern, especially given the aging world population. To evaluate the process of skeletal muscle injury and compare it with muscle lesions observed in humans, we developed a novel in vivo
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Sports-related muscle injuries account for 10–55% of all injuries, which is a growing concern, especially given the aging world population. To evaluate the process of skeletal muscle injury and compare it with muscle lesions observed in humans, we developed a novel in vivo model in sheep. In this model, muscle injury was induced by an ultrasound-guided transverse biopsy at the myotendinous junction of the medial gastrocnemius muscle. Twelve male sheep were examined at 3, 7, 14, and 28 days post-injury. Histological, immunofluorescence, and MRI analyses indicate that our sheep model could resemble key human clinicopathological features. Statistically significant differences (p < 0.05) were observed in collagen I, dMHC, α-SMA, and CD68 immunohistochemical detection when comparing injured and healthy muscles. The injured gastrocnemius muscle exhibited elevated levels of type I collagen, infiltration of CD68(+) macrophages, angiogenesis, and the emergence of newly regenerated dMHC(+) myofibers, which persisted for up to 4 weeks post-injury. Similarly, the progression of muscle injury in the sheep model was assessed using advanced clinical 3 T MRI and compared with MRI scans from human patients. The data indicate that the sheep muscle injury model presents features similar to those observed in human skeletal muscle injuries. This makes it a valuable large animal model for studying muscle injuries and developing novel therapeutic strategies.
Full article
(This article belongs to the Special Issue Molecular Research on Skeletal Muscle Diseases)
Open AccessArticle
Evaluating the Impact of Probiotic Therapy on the Endocannabinoid System, Pain, Sleep and Fatigue: A Randomized, Double-Blind, Placebo-Controlled Trial in Dancers
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Jakub Wiącek, Tomasz Podgórski, Krzysztof Kusy, Igor Łoniewski, Karolina Skonieczna-Żydecka and Joanna Karolkiewicz
Int. J. Mol. Sci. 2024, 25(11), 5611; https://doi.org/10.3390/ijms25115611 (registering DOI) - 21 May 2024
Abstract
Emerging research links the endocannabinoid system to gut microbiota, influencing nociception, mood, and immunity, yet the molecular interactions remain unclear. This study focused on the effects of probiotics on ECS markers—cannabinoid receptor type 2 (CB2) and fatty acid amide hydrolase (FAAH)—in dancers, a
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Emerging research links the endocannabinoid system to gut microbiota, influencing nociception, mood, and immunity, yet the molecular interactions remain unclear. This study focused on the effects of probiotics on ECS markers—cannabinoid receptor type 2 (CB2) and fatty acid amide hydrolase (FAAH)—in dancers, a group selected due to their high exposure to physical and psychological stress. In a double-blind, placebo-controlled trial (ClinicalTrials.gov NCT05567653), 15 dancers were assigned to receive either a 12-week regimen of Lactobacillus helveticus Rosell-52 and Bifidobacterium longum Rosell-17 or a placebo (PLA: n = 10, PRO: n = 5). There were no significant changes in CB2 (probiotic: 0.55 to 0.29 ng/mL; placebo: 0.86 to 0.72 ng/mL) or FAAH levels (probiotic: 5.93 to 6.02 ng/mL; placebo: 6.46 to 6.94 ng/mL; p > 0.05). A trend toward improved sleep quality was observed in the probiotic group, while the placebo group showed a decline (PRO: from 1.4 to 1.0; PLA: from 0.8 to 1.2; p = 0.07841). No other differences were noted in assessed outcomes (pain and fatigue). Probiotic supplementation showed no significant impact on CB2 or FAAH levels, pain, or fatigue but suggested potential benefits for sleep quality, suggesting an area for further research.
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(This article belongs to the Special Issue Gut Microbiota and Nutrition in Human Health)
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Immunophenotypic but Not Genetic Changes Reclassify the Majority of Relapsed/Refractory Pediatric Cases of Early T-Cell Precursor Acute Lymphoblastic Leukemia
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Irina Demina, Aya Dagestani, Aleksandra Borkovskaia, Alexandra Semchenkova, Olga Soldatkina, Svetlana Kashpor, Yulia Olshanskaya, Julia Roumiantseva, Alexander Karachunskiy, Galina Novichkova, Michael Maschan, Elena Zerkalenkova and Alexander Popov
Int. J. Mol. Sci. 2024, 25(11), 5610; https://doi.org/10.3390/ijms25115610 (registering DOI) - 21 May 2024
Abstract
Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) develops from very early cells with the potential for both T-cell and myeloid differentiation. The ambiguous nature of leukemic blasts in ETP-ALL may lead to immunophenotypic alterations at relapse. Here, we address immunophenotypic alterations and related
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Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) develops from very early cells with the potential for both T-cell and myeloid differentiation. The ambiguous nature of leukemic blasts in ETP-ALL may lead to immunophenotypic alterations at relapse. Here, we address immunophenotypic alterations and related classification issues, as well as genetic features of relapsed pediatric ETP-ALL. Between 2017 and 2022, 7518 patients were diagnosed with acute leukemia (AL). In addition to conventional immunophenotyping, karyotyping, and FISH studies, we performed next-generation sequencing of the T-cell receptor clonal repertoire and reverse transcription PCR and RNA sequencing for patients with ETP-ALL at both initial diagnosis and relapse. Among a total of 534 patients diagnosed with T-cell ALL (7.1%), 60 had ETP-ALL (11.2%). Ten patients with ETP-ALL experienced relapse or progression on therapy (16.7%), with a median time to event of 5 months (ranging from two weeks to 5 years). Most relapses were classified as AL of ambiguous lineage (n = 5) and acute myeloid leukemia (AML) (n = 4). Major genetic markers of leukemic cells remained unchanged at relapse. Of the patients with relapse, four had polyclonal leukemic populations and a relapse with AML or bilineal mixed-phenotype AL (MPAL). Three patients had clonal TRD rearrangements and relapse with AML, undifferentiated AL, or retention of the ETP-ALL phenotype. ETP-ALL relapse requires careful clinical and laboratory diagnosis. Treatment decisions should rely mainly on initial examination data, taking into account both immunophenotypic and molecular/genetic characteristics.
Full article
(This article belongs to the Special Issue Molecular Aspects of Hematological Malignancies and Benign Hematological Disorders 2.0)
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Unveiling the Nature and Strength of Selenium-Centered Chalcogen Bonds in Binary Complexes of SeO2 with Oxygen-/Sulfur-Containing Lewis Bases: Insights from Theoretical Calculations
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Tao Lu, Renhua Chen, Qingyu Liu, Yeshuang Zhong, Fengying Lei and Zhu Zeng
Int. J. Mol. Sci. 2024, 25(11), 5609; https://doi.org/10.3390/ijms25115609 (registering DOI) - 21 May 2024
Abstract
Among various non-covalent interactions, selenium-centered chalcogen bonds (SeChBs) have garnered considerable attention in recent years as a result of their important contributions to crystal engineering, organocatalysis, molecular recognition, materials science, and biological systems. Herein, we systematically investigated π–hole-type Se∙∙∙O/S ChBs in
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Among various non-covalent interactions, selenium-centered chalcogen bonds (SeChBs) have garnered considerable attention in recent years as a result of their important contributions to crystal engineering, organocatalysis, molecular recognition, materials science, and biological systems. Herein, we systematically investigated π–hole-type Se∙∙∙O/S ChBs in the binary complexes of SeO2 with a series of O-/S-containing Lewis bases by means of high-level ab initio computations. The results demonstrate that there exists an attractive interaction between the Se atom of SeO2 and the O/S atom of Lewis bases. The interaction energies computed at the MP2/aug-cc-pVTZ level range from −4.68 kcal/mol to −10.83 kcal/mol for the Se∙∙∙O chalcogen-bonded complexes and vary between −3.53 kcal/mol and −13.77 kcal/mol for the Se∙∙∙S chalcogen-bonded complexes. The Se∙∙∙O/S ChBs exhibit a relatively short binding distance in comparison to the sum of the van der Waals radii of two chalcogen atoms. The Se∙∙∙O/S ChBs in all of the studied complexes show significant strength and a closed-shell nature, with a partially covalent character in most cases. Furthermore, the strength of these Se∙∙∙O/S ChBs generally surpasses that of the C/O–H∙∙∙O hydrogen bonds within the same complex. It should be noted that additional C/O–H∙∙∙O interactions have a large effect on the geometric structures and strength of Se∙∙∙O/S ChBs. Two subunits are connected together mainly via the orbital interaction between the lone pair of O/S atoms in the Lewis bases and the BD*(OSe) anti-bonding orbital of SeO2, except for the SeO2∙∙∙HCSOH complex. The electrostatic component emerges as the largest attractive contributor for stabilizing the examined complexes, with significant contributions from induction and dispersion components as well.
Full article
(This article belongs to the Special Issue Chemical Bond and Bonding: Fundamental Aspects and Recent Developments)
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Interplay between the Chaperone System and Gut Microbiota Dysbiosis in Systemic Lupus Erythematosus Pathogenesis: Is Molecular Mimicry the Missing Link between Those Two Factors?
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Alessandra Maria Vitale, Letizia Paladino, Celeste Caruso Bavisotto, Rosario Barone, Francesca Rappa, Everly Conway de Macario, Francesco Cappello, Alberto J. L. Macario and Antonella Marino Gammazza
Int. J. Mol. Sci. 2024, 25(11), 5608; https://doi.org/10.3390/ijms25115608 (registering DOI) - 21 May 2024
Abstract
Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease characterized by self-immune tolerance breakdown and the production of autoantibodies, causing the deposition of immune complexes and triggering inflammation and immune-mediated damage. SLE pathogenesis involves genetic predisposition and a combination of environmental factors. Clinical
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Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease characterized by self-immune tolerance breakdown and the production of autoantibodies, causing the deposition of immune complexes and triggering inflammation and immune-mediated damage. SLE pathogenesis involves genetic predisposition and a combination of environmental factors. Clinical manifestations are variable, making an early diagnosis challenging. Heat shock proteins (Hsps), belonging to the chaperone system, interact with the immune system, acting as pro-inflammatory factors, autoantigens, as well as immune tolerance promoters. Increased levels of some Hsps and the production of autoantibodies against them are correlated with SLE onset and progression. The production of these autoantibodies has been attributed to molecular mimicry, occurring upon viral and bacterial infections, since they are evolutionary highly conserved. Gut microbiota dysbiosis has been associated with the occurrence and severity of SLE. Numerous findings suggest that proteins and metabolites of commensal bacteria can mimic autoantigens, inducing autoimmunity, because of molecular mimicry. Here, we propose that shared epitopes between human Hsps and those of gut commensal bacteria cause the production of anti-Hsp autoantibodies that cross-react with human molecules, contributing to SLE pathogenesis. Thus, the involvement of the chaperone system, gut microbiota dysbiosis, and molecular mimicry in SLE ought to be coordinately studied.
Full article
(This article belongs to the Special Issue Immune Mechanisms and Biomarkers in Systemic Lupus Erythematosus)
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Clinical Significance of the Plasma Biomarker Panels in Amyloid-Negative and Tau PET-Positive Amnestic Patients: Comparisons with Alzheimer’s Disease and Unimpaired Cognitive Controls
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Hsin-I Chang, Kuo-Lun Huang, Chung-Gue Huang, Chi-Wei Huang, Shu-Hua Huang, Kun-Ju Lin and Chiung-Chih Chang
Int. J. Mol. Sci. 2024, 25(11), 5607; https://doi.org/10.3390/ijms25115607 (registering DOI) - 21 May 2024
Abstract
The purpose of this study was to investigate whether plasma biomarkers can help to diagnose, differentiate from Alzheimer disease (AD), and stage cognitive performance in patients with positron emission tomography (PET)-confirmed primary age-related tauopathy, termed tau-first cognitive proteinopathy (TCP) in this study. In
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The purpose of this study was to investigate whether plasma biomarkers can help to diagnose, differentiate from Alzheimer disease (AD), and stage cognitive performance in patients with positron emission tomography (PET)-confirmed primary age-related tauopathy, termed tau-first cognitive proteinopathy (TCP) in this study. In this multi-center study, we enrolled 285 subjects with young-onset AD (YOAD; n = 55), late-onset AD (LOAD; n = 96), TCP (n = 44), and cognitively unimpaired controls (CTL; n = 90) and analyzed plasma Aβ42/Aβ40, pTau181, neurofilament light (NFL), and total-tau using single-molecule assays. Amyloid and tau centiloids reflected pathological burden, and hippocampal volume reflected structural integrity. Receiver operating characteristic curves and areas under the curves (AUCs) were used to determine the diagnostic accuracy of plasma biomarkers compared to hippocampal volume and amyloid and tau centiloids. The Mini-Mental State Examination score (MMSE) served as the major cognitive outcome. Logistic stepwise regression was used to assess the overall diagnostic accuracy, combining fluid and structural biomarkers and a stepwise linear regression model for the significant variables for MMSE. For TCP, tau centiloid reached the highest AUC for diagnosis (0.79), while pTau181 could differentiate TCP from YOAD (accuracy 0.775) and LOAD (accuracy 0.806). NFL reflected the clinical dementia rating in TCP, while pTau181 (rho = 0.3487, p = 0.03) and Aβ42/Aβ40 (rho = −0.36, p = 0.02) were significantly correlated with tau centiloid. Hippocampal volume (unstandardized β = 4.99, p = 0.01) outperformed all of the fluid biomarkers in predicting MMSE scores in the TCP group. Our results support the superiority of tau PET to diagnose TCP, pTau181 to differentiate TCP from YOAD or LOAD, and NFL for functional staging.
Full article
(This article belongs to the Special Issue Circulating Biomarkers for the Diagnosis of Neurobiological Diseases)
Open AccessArticle
The Intramolecular Charge Transfer Mechanism by Which Chiral Self-Assembled H8-BINOL Vesicles Enantioselectively Recognize Amino Alcohols
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Rong Wang, Kaiyue Song, Zhaoqin Wei, Yue Sun, Xiaoxia Sun and Yu Hu
Int. J. Mol. Sci. 2024, 25(11), 5606; https://doi.org/10.3390/ijms25115606 (registering DOI) - 21 May 2024
Abstract
The chiral H8-BINOL derivatives R-1 and R-2 were efficiently synthesized via a Suzuki coupling reaction, and they can be used as novel dialdehyde fluorescent probes for the enantioselective recognition of R/S-2-amino-1-phenylethanol. In addition, R-1 is much more effective than R-2. Scanning
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The chiral H8-BINOL derivatives R-1 and R-2 were efficiently synthesized via a Suzuki coupling reaction, and they can be used as novel dialdehyde fluorescent probes for the enantioselective recognition of R/S-2-amino-1-phenylethanol. In addition, R-1 is much more effective than R-2. Scanning electron microscope images and X-ray analyses show that R-1 can form supramolecular vesicles through the self-assembly effect of the π-π force and strong hydrogen bonding. As determined via analysis, the fluorescence of the probe was significantly enhanced by mixing a small amount of S-2-amino-1-phenylethanol into R-1, with a redshift of 38 nm, whereas no significant fluorescence response was observed in R-2-amino-1-phenylethanol. The enantioselective identification of S-2-amino-1-phenylethanol by the probe R-1 was further investigated through nuclear magnetic titration and fluorescence kinetic experiments and DFT calculations. The results showed that this mechanism was not only a simple reactive probe but also realized object recognition through an ICT mechanism. As the intramolecular hydrogen bond activated the carbonyl group on the probe R-1, the carbonyl carbon atom became positively charged. As a strong nucleophile, the amino group of S-2-amino-1-phenylethanol first transferred the amino electrons to a carbonyl carbocation, resulting in a significantly enhanced fluorescence of the probe R-1 and a 38 nm redshift. Similarly, S-2-amino-1-phenylethanol alone caused severe damage to the self-assembled vesicle structure of the probe molecule itself due to its spatial structure, which made R-1 highly enantioselective towards it.
Full article
(This article belongs to the Special Issue Recent Advances in Luminescence: From Mechanisms to Applications)
Open AccessReview
Prg4-Expressing Chondroprogenitor Cells in the Superficial Zone of Articular Cartilage
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Nadezda Ignatyeva, Nikita Gavrilov, Peter S. Timashev and Ekaterina V. Medvedeva
Int. J. Mol. Sci. 2024, 25(11), 5605; https://doi.org/10.3390/ijms25115605 (registering DOI) - 21 May 2024
Abstract
Joint-resident chondrogenic precursor cells have become a significant therapeutic option due to the lack of regenerative capacity in articular cartilage. Progenitor cells are located in the superficial zone of the articular cartilage, producing lubricin/Prg4 to decrease friction of cartilage surfaces during joint movement.
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Joint-resident chondrogenic precursor cells have become a significant therapeutic option due to the lack of regenerative capacity in articular cartilage. Progenitor cells are located in the superficial zone of the articular cartilage, producing lubricin/Prg4 to decrease friction of cartilage surfaces during joint movement. Prg4-positive progenitors are crucial in maintaining the joint’s structure and functionality. The disappearance of progenitor cells leads to changes in articular hyaline cartilage over time, subchondral bone abnormalities, and the formation of ectopic ossification. Genetic labeling cell technology has been the main tool used to characterize Prg4-expressing progenitor cells of articular cartilage in vivo through drug injection at different time points. This technology allows for the determination of the origin of progenitor cells and the tracking of their progeny during joint development and cartilage damage. We endeavored to highlight the currently known information about the Prg4-producing cell population in the joint to underline the significance of the role of these cells in the development of articular cartilage and its homeostasis. This review focuses on superficial progenitors in the joint, how they contribute to postnatal articular cartilage formation, their capacity for regeneration, and the consequences of Prg4 deficiency in these cells. We have accumulated information about the Prg4+ cell population of articular cartilage obtained through various elegantly designed experiments using transgenic technologies to identify potential opportunities for further research.
Full article
(This article belongs to the Special Issue Molecular Aspects of Cartilage Biology)
Open AccessReview
The Biological Role of Platelet Derivatives in Regenerative Aesthetics
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Lorena Cristina Santos, Giselle Lobo Lana, Gabriel Silva Santos, Silvia Beatriz Coutinho Visoni, Rayssa Junqueira Brigagão, Napoliane Santos, Rafaela Sobreiro, Andreza da Cruz Silva Reis, Bruno Lima Rodrigues, Sabrina Ferrari, Claudia Herrera Tambeli and José Fábio Lana
Int. J. Mol. Sci. 2024, 25(11), 5604; https://doi.org/10.3390/ijms25115604 (registering DOI) - 21 May 2024
Abstract
Bioproducts derived from platelets have been extensively used across various medical fields, with a recent notable surge in their application in dermatology and aesthetic procedures. These products, such as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), play crucial roles in inducing blood vessel
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Bioproducts derived from platelets have been extensively used across various medical fields, with a recent notable surge in their application in dermatology and aesthetic procedures. These products, such as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), play crucial roles in inducing blood vessel proliferation through growth factors derived from peripheral blood. PRP and PRF, in particular, facilitate fibrin polymerization, creating a robust structure that serves as a reservoir for numerous growth factors. These factors contribute to tissue regeneration by promoting cell proliferation, differentiation, and migration and collagen/elastin production. Aesthetic medicine harnesses these effects for diverse purposes, including hair restoration, scar treatment, striae management, and wound healing. Furthermore, these biological products can act as adjuvants with other treatment modalities, such as laser therapy, radiofrequency, and microneedling. This review synthesizes the existing evidence, offering insights into the applications and benefits of biological products in aesthetic medicine.
Full article
(This article belongs to the Special Issue Research and Application of Platelet-Rich Plasma (PRP))
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Open AccessArticle
MS785-MS27 Reactive Misfolded/Non-Native Zn-Deficient SOD1 Species Exhibit Cytotoxicity and Adopt Heterozygous Conformations in Motor Neurons
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Eiichi Tokuda, Yume Sakashita, Naoya Tokoro, Ayano Date, Yasuhiro Kosuge and Tomohiro Miyasaka
Int. J. Mol. Sci. 2024, 25(11), 5603; https://doi.org/10.3390/ijms25115603 (registering DOI) - 21 May 2024
Abstract
Misfolding of superoxide dismutase-1 (SOD1) is a pathological hallmark of amyotrophic lateral sclerosis (ALS) with SOD1 mutations. The development of antibodies specific for misfolded SOD1 deepens our understanding of how the protein participates in ALS pathogenesis. Since the term “misfolding” refers to various
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Misfolding of superoxide dismutase-1 (SOD1) is a pathological hallmark of amyotrophic lateral sclerosis (ALS) with SOD1 mutations. The development of antibodies specific for misfolded SOD1 deepens our understanding of how the protein participates in ALS pathogenesis. Since the term “misfolding” refers to various disordered conformers other than the natively folded one, which misfolded species are recognized by specific antibodies should be determined. Here, we molecularly characterized the recognition by MS785-MS27, an antibody cocktail experimentally confirmed to recognize over 100 ALS-linked SOD1 mutants. Indirect ELISA revealed that the antibody cocktail recognized Zn-deficient wild-type and mutated SOD1 species. It also recognized conformation-disordered wild-type and mutated SOD1 species, such as unfolded and oligomeric forms, but had less affinity for the aggregated form. Antibody-reactive SOD1 exhibited cytotoxicity to a motor neuron cell model, which was blocked by Zn treatment with Zn-deficient SOD1. Immunohistochemistry revealed antibody-reactive SOD1 mainly in spinal motor neurons of SOD1G93A mice throughout the disease course, and the distribution after symptomatic stages differed from that of other misfolded SOD1 species. This suggests that misfolded/non-native SOD1 species exist as heterogeneous populations. In conclusion, MS785-MS27 recognizes various conformation-disordered SOD1 species lacking the Zn ion.
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(This article belongs to the Section Molecular Neurobiology)
Open AccessArticle
A Spatio-Temporal-Dependent Requirement of Sonic Hedgehog in the Early Development of Sclerotome-Derived Vertebrae and Ribs
by
Nitza Kahane, Yael Zohara Dahan-Barda and Chaya Kalcheim
Int. J. Mol. Sci. 2024, 25(11), 5602; https://doi.org/10.3390/ijms25115602 (registering DOI) - 21 May 2024
Abstract
Derived from axial structures, Sonic Hedgehog (Shh) is secreted into the paraxial mesoderm, where it plays crucial roles in sclerotome induction and myotome differentiation. Through conditional loss-of-function in quail embryos, we investigate the timing and impact of Shh activity during early formation of
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Derived from axial structures, Sonic Hedgehog (Shh) is secreted into the paraxial mesoderm, where it plays crucial roles in sclerotome induction and myotome differentiation. Through conditional loss-of-function in quail embryos, we investigate the timing and impact of Shh activity during early formation of sclerotome-derived vertebrae and ribs, and of lateral mesoderm-derived sternum. To this end, Hedgehog interacting protein (Hhip) was electroporated at various times between days 2 and 5. While the vertebral body and rib primordium showed consistent size reduction, rib expansion into the somatopleura remained unaffected, and the sternal bud developed normally. Additionally, we compared these effects with those of locally inhibiting BMP activity. Transfection of Noggin in the lateral mesoderm hindered sternal bud formation. Unlike Hhip, BMP inhibition via Noggin or Smad6 induced myogenic differentiation of the lateral dermomyotome lip, while impeding the growth of the myotome/rib complex into the somatic mesoderm, thus affirming the role of the lateral dermomyotome epithelium in rib guidance. Overall, these findings underscore the continuous requirement for opposing gradients of Shh and BMP activity in the morphogenesis of proximal and distal flank skeletal structures, respectively. Future research should address the implications of these early interactions to the later morphogenesis and function of the musculo-skeletal system and of possible associated malformations.
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(This article belongs to the Collection Feature Papers in “Molecular Biology”)
Open AccessReview
The Basic Requirement of Tight Junction Proteins in Blood-Brain Barrier Function and Their Role in Pathologies
by
Sophie Dithmer, Ingolf E. Blasig, Paul A. Fraser, Zhihai Qin and Reiner F. Haseloff
Int. J. Mol. Sci. 2024, 25(11), 5601; https://doi.org/10.3390/ijms25115601 (registering DOI) - 21 May 2024
Abstract
This review addresses the role of tight junction proteins at the blood-brain barrier (BBB). Their expression is described, and their role in physiological and pathological processes at the BBB is discussed. Based on this, new approaches are depicted for paracellular drug delivery and
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This review addresses the role of tight junction proteins at the blood-brain barrier (BBB). Their expression is described, and their role in physiological and pathological processes at the BBB is discussed. Based on this, new approaches are depicted for paracellular drug delivery and diagnostics in the treatment of cerebral diseases. Recent data provide convincing evidence that, in addition to its impairment in the course of diseases, the BBB could be involved in the aetiology of CNS disorders. Further progress will be expected based on new insights in tight junction protein structure and in their involvement in signalling pathways.
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(This article belongs to the Special Issue The Tight Junction and Its Proteins: From Structure to Pathologies)
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Open AccessArticle
Hydrogel Formulation for Biomimetic Fibroblast Cell Culture: Exploring Effects of External Stresses and Cellular Responses
by
Immacolata Greco, Hatim Machrafi, Christophe Minetti, Chiara Risaliti, Allegra Bandini, Francesca Cialdai, Monica Monici and Carlo S. Iorio
Int. J. Mol. Sci. 2024, 25(11), 5600; https://doi.org/10.3390/ijms25115600 - 21 May 2024
Abstract
In the process of tissue engineering, several types of stresses can influence the outcome of tissue regeneration. This outcome can be understood by designing hydrogels that mimic this process and studying how such hydrogel scaffolds and cells behave under a set of stresses.
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In the process of tissue engineering, several types of stresses can influence the outcome of tissue regeneration. This outcome can be understood by designing hydrogels that mimic this process and studying how such hydrogel scaffolds and cells behave under a set of stresses. Here, a hydrogel formulation is proposed to create biomimetic scaffolds suitable for fibroblast cell culture. Subsequently, we examine the impact of external stresses on fibroblast cells cultured on both solid and porous hydrogels. These stresses included mechanical tension and altered-gravity conditions experienced during the 83rd parabolic flight campaign conducted by the European Space Agency. This study shows distinct cellular responses characterized by cell aggregation and redistribution in regions of intensified stress concentration. This paper presents a new biomimetic hydrogel that fulfills tissue-engineering requirements in terms of biocompatibility and mechanical stability. Moreover, it contributes to our comprehension of cellular biomechanics under diverse gravitational conditions, shedding light on the dynamic cellular adaptations versus varying stress environments.
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(This article belongs to the Special Issue Research on Bio-Scaffold for Tissue Engineering)
Open AccessArticle
Use of Aloe Vera Gel as Media to Assess Antimicrobial Activity and Development of Antimicrobial Nanocomposites
by
Erwan Rauwel, Geeta Arya, Kristi Praakle and Protima Rauwel
Int. J. Mol. Sci. 2024, 25(11), 5599; https://doi.org/10.3390/ijms25115599 - 21 May 2024
Abstract
Antimicrobial resistance is a menace to public health on a global scale. In this regard, nanomaterials exhibiting antimicrobial properties represent a promising solution. Both metal and metal oxide nanomaterials are suitable candidates, even though their mechanisms of action vary. Multiple antimicrobial mechanisms can
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Antimicrobial resistance is a menace to public health on a global scale. In this regard, nanomaterials exhibiting antimicrobial properties represent a promising solution. Both metal and metal oxide nanomaterials are suitable candidates, even though their mechanisms of action vary. Multiple antimicrobial mechanisms can occur simultaneously or independently; this includes either direct contact with the pathogens, nanomaterial uptake, oxidative stress, ion release, or any of their combinations. However, due to their specific properties and more particularly fast settling, existing methods to study the antimicrobial properties of nanoparticles have not been specifically adapted in some cases. The development of methodologies that can assess the antimicrobial properties of metallic nanomaterials accurately is necessary. A cost-effective methodology with a straightforward set-up that enables the easy and quick assessment of the antimicrobial properties of metal nanoparticles with high accuracy has been developed. The methodology is also capable of confirming whether the killing mechanism involves ionic diffusion. Finally, Aloe Vera gel showed good properties for use as a medium for the development of antimicrobial ointment.
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(This article belongs to the Special Issue The Advances in Antimicrobial Biomaterials)
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Open AccessArticle
Ace Deficiency Induces Intestinal Inflammation in Zebrafish
by
Mingxia Wei, Qinqing Yu, Enguang Li, Yibing Zhao, Chen Sun, Hongyan Li, Zhenhui Liu and Guangdong Ji
Int. J. Mol. Sci. 2024, 25(11), 5598; https://doi.org/10.3390/ijms25115598 - 21 May 2024
Abstract
Inflammatory bowel disease (IBD) is a nonspecific chronic inflammatory disease resulting from an immune disorder in the intestine that is prone to relapse and incurable. The understanding of the pathogenesis of IBD remains unclear. In this study, we found that ace (angiotensin-converting enzyme),
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Inflammatory bowel disease (IBD) is a nonspecific chronic inflammatory disease resulting from an immune disorder in the intestine that is prone to relapse and incurable. The understanding of the pathogenesis of IBD remains unclear. In this study, we found that ace (angiotensin-converting enzyme), expressed abundantly in the intestine, plays an important role in IBD. The deletion of ace in zebrafish caused intestinal inflammation with increased expression of the inflammatory marker genes interleukin 1 beta (il1b), matrix metallopeptidase 9 (mmp9), myeloid-specific peroxidase (mpx), leukocyte cell-derived chemotaxin-2-like (lect2l), and chemokine (C-X-C motif) ligand 8b (cxcl8b). Moreover, the secretion of mucus in the ace−/− mutants was significantly higher than that in the wild-type zebrafish, validating the phenotype of intestinal inflammation. This was further confirmed by the IBD model constructed using dextran sodium sulfate (DSS), in which the mutant zebrafish had a higher susceptibility to enteritis. Our study reveals the role of ace in intestinal homeostasis, providing a new target for potential therapeutic interventions.
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(This article belongs to the Special Issue Zebrafish: A Model Organism for Human Health and Disease)
Open AccessReview
Unraveling the Keratin Expression in Oral Leukoplakia: A Scoping Review
by
Guru Murthy O, Jeremy Lau, Ramesh Balasubramaniam, Agnieszka M. Frydrych and Omar Kujan
Int. J. Mol. Sci. 2024, 25(11), 5597; https://doi.org/10.3390/ijms25115597 - 21 May 2024
Abstract
Intermediate filaments are one of three polymeric structures that form the cytoskeleton of epithelial cells. In the epithelium, these filaments are made up of a variety of keratin proteins. Intermediate filaments complete a wide range of functions in keratinocytes, including maintaining cell structure,
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Intermediate filaments are one of three polymeric structures that form the cytoskeleton of epithelial cells. In the epithelium, these filaments are made up of a variety of keratin proteins. Intermediate filaments complete a wide range of functions in keratinocytes, including maintaining cell structure, cell growth, cell proliferation, cell migration, and more. Given that these functions are intimately associated with the carcinogenic process, and that hyperkeratinization is a quintessential feature of oral leukoplakias, the utility of keratins in oral leukoplakia is yet to be fully explored. This scoping review aims to outline the current knowledge founded on original studies on human tissues regarding the expression and utility of keratins as diagnostic, prognostic, and predictive biomarkers in oral leukoplakias. After using a search strategy developed for several scientific databases, namely, PubMed, Scopus, Web of Science, and OVID, 42 papers met the inclusion and exclusion criteria. One more article was added when it was identified through manually searching the list of references. The included papers were published between 1989 and 2024. Keratins 1–20 were investigated in the 43 included studies, and their expression was assessed in oral leukoplakia and dysplasia cases. Only five studies investigated the prognostic role of keratins in relation to malignant transformation. No studies evaluated keratins as a diagnostic adjunct or predictive tool. Evidence supports the idea that dysplasia disrupts the terminal differentiation pathway of primary keratins. Gain of keratin 17 expression and loss of keratin 13 were significantly observed in differentiated epithelial dysplasia. Also, the keratin 19 extension into suprabasal cells has been associated with the evolving features of dysplasia. The loss of keratin1/keratin 10 has been significantly associated with high-grade dysplasia. The prognostic value of cytokeratins has shown conflicting results, and further studies are required to ascertain their role in predicting the malignant transformation of oral leukoplakia.
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(This article belongs to the Special Issue Oral Cancer and Disease in Humans and Animals)
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