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
Recent Advances in the Field of Amino Acid-Conjugated Aminoferrocenes—A Personal Perspective
Int. J. Mol. Sci. 2024, 25(9), 4810; https://doi.org/10.3390/ijms25094810 (registering DOI) - 28 Apr 2024
Abstract
The development of turn-based inhibitors of protein–protein interactions has attracted considerable attention in medicinal chemistry. Our group has synthesized a series of peptides derived from an amino-functionalized ferrocene to investigate their potential to mimic protein turn structures. Detailed DFT and spectroscopic studies (IR,
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The development of turn-based inhibitors of protein–protein interactions has attracted considerable attention in medicinal chemistry. Our group has synthesized a series of peptides derived from an amino-functionalized ferrocene to investigate their potential to mimic protein turn structures. Detailed DFT and spectroscopic studies (IR, NMR, CD) have shown that, for peptides, the backbone chirality and bulkiness of the amino acid side chains determine the hydrogen-bond pattern, allowing tuning of the size of the preferred hydrogen-bonded ring in turn-folded structures. However, their biological potential is more dependent on their lipophilicity. In addition, our pioneering work on the chiroptical properties of aminoferrocene-containing peptides enables the correlation of their geometry with the sign of the CD signal in the absorption region of the ferrocene chromophore. These studies have opened up the possibility of using aminoferrocene and its derivatives as chirooptical probes for the determination of various chirality elements, such as the central chirality of amino acids and the helicity of peptide sequences.
Full article
(This article belongs to the Special Issue Synthesis, Properties and Biological Evaluation of Ferrocene-Modified Peptides and Biomolecules)
Open AccessReview
Antisense Oligonucleotides (ASOs) in Motor Neuron Diseases: A Road to Cure in Light and Shade
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Silvia Cantara, Giorgia Simoncelli and Claudia Ricci
Int. J. Mol. Sci. 2024, 25(9), 4809; https://doi.org/10.3390/ijms25094809 (registering DOI) - 28 Apr 2024
Abstract
Antisense oligonucleotides (ASOs) are short oligodeoxynucleotides designed to bind to specific regions of target mRNA. ASOs can modulate pre-mRNA splicing, increase levels of functional proteins, and decrease levels of toxic proteins. ASOs are being developed for the treatment of motor neuron diseases (MNDs),
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Antisense oligonucleotides (ASOs) are short oligodeoxynucleotides designed to bind to specific regions of target mRNA. ASOs can modulate pre-mRNA splicing, increase levels of functional proteins, and decrease levels of toxic proteins. ASOs are being developed for the treatment of motor neuron diseases (MNDs), including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA). The biggest success has been the ASO known as nusinersen, the first effective therapy for SMA, able to improve symptoms and slow disease progression. Another success is tofersen, an ASO designed to treat ALS patients with SOD1 gene mutations. Both ASOs have been approved by the FDA and EMA. On the other hand, ASO treatment in ALS patients with the C9orf72 gene mutation did not show any improvement in disease progression. The aim of this review is to provide an up-to-date overview of ASO research in MNDs, from preclinical studies to clinical trials and, where available, regulatory approval. We highlight the successes and failures, underline the strengths and limitations of the current ASO research, and suggest possible approaches that could lead to more effective treatments.
Full article
(This article belongs to the Special Issue Neurodegenerative Disease: From Molecular Basis to Therapy, 2nd Edition)
Open AccessReview
Balancing Benefits and Risks: A Literature Review on Hypersensitivity Reactions to Human G-CSF (Granulocyte Colony-Stimulating Factor)
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Roxana Silvia Bumbăcea, Mihaela Ruxandra Udrea, Selda Ali and Violeta Claudia Bojincă
Int. J. Mol. Sci. 2024, 25(9), 4807; https://doi.org/10.3390/ijms25094807 (registering DOI) - 28 Apr 2024
Abstract
Human granulocyte colony-stimulating factor (G-CSF) is a granulopoietic growth factor used in the treatment of neutropenia following chemotherapy, myeloablative treatment, or healthy donors preparing for allogeneic transplantation. Few hypersensitivity reactions (HRs) have been reported, and its true prevalence is unknown. We aimed to
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Human granulocyte colony-stimulating factor (G-CSF) is a granulopoietic growth factor used in the treatment of neutropenia following chemotherapy, myeloablative treatment, or healthy donors preparing for allogeneic transplantation. Few hypersensitivity reactions (HRs) have been reported, and its true prevalence is unknown. We aimed to systematically characterize G-CSF-induced HRs while including a comprehensive list of adverse reactions. We reviewed articles published before January 2024 by searching in the PubMed, Embase, Cochrane Library, and Web of Science databases using a combination of the keywords listed, selected the ones needed, and extracted relevant data. The search resulted in 68 entries, 17 relevant to our study and 7 others found from manually searching bibliographic sources. A total of 40 cases of G-CSF-induced HR were described and classified as immediate (29) or delayed (11). Immediate ones were mostly caused by filgrastim (13 minimum), with at least 9 being grade 5 on the WAO anaphylaxis scale. Delayed reactions were mostly maculopapular exanthemas and allowed for the continuation of G-CSF. Reactions after first exposure frequently appeared and were present in at least 11 of the 40 cases. Only five desensitization protocols have been found concerning the topic at hand in the analyzed data. We believe this study brings to light the research interest in this topic that could benefit from further exploration, and propose regular updating to include the most recently published evidence.
Full article
(This article belongs to the Special Issue Drug Hypersensitivity Reactions and Pseudoallergy: A Moving Frontline in Allergy Research)
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Role of Calcitriol and Vitamin D Receptor (VDR) Gene Polymorphisms in Alzheimer’s Disease
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Soon Pyo Jeong, Niti Sharma and Seong Soo A. An
Int. J. Mol. Sci. 2024, 25(9), 4806; https://doi.org/10.3390/ijms25094806 (registering DOI) - 28 Apr 2024
Abstract
Alzheimer’s disease (AD) is characterized by amyloid beta (Aβ) buildup and neuronal degeneration. An association between low serum vitamin D levels and an increased risk of AD has been reported in several epidemiological studies. Calcitriol (1,25-dihydroxycholecalciferol) is the active form of vitamin D,
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Alzheimer’s disease (AD) is characterized by amyloid beta (Aβ) buildup and neuronal degeneration. An association between low serum vitamin D levels and an increased risk of AD has been reported in several epidemiological studies. Calcitriol (1,25-dihydroxycholecalciferol) is the active form of vitamin D, and is generated in the kidney and many other tissues/organs, including the brain. It is a steroid hormone that regulates important functions like calcium/phosphorous levels, bone mineralization, and immunomodulation, indicating its broader systemic significance. In addition, calcitriol confers neuroprotection by mitigating oxidative stress and neuroinflammation, promoting the clearance of Aβ, myelin formation, neurogenesis, neurotransmission, and autophagy. The receptors to which calcitriol binds (vitamin D receptors; VDRs) to exert its effects are distributed over many organs and tissues, representing other significant roles of calcitriol beyond sustaining bone health. The biological effects of calcitriol are manifested through genomic (classical) and non-genomic actions through different pathways. The first is a slow genomic effect involving nuclear VDR directly affecting gene transcription. The association of AD with VDR gene polymorphisms relies on the changes in vitamin D consumption, which lowers VDR expression, protein stability, and binding affinity. It leads to the altered expression of genes involved in the neuroprotective effects of calcitriol. This review summarizes the neuroprotective mechanism of calcitriol and the role of VDR polymorphisms in AD, and might help develop potential therapeutic strategies and markers for AD in the future.
Full article
(This article belongs to the Special Issue Vitamin D and Vitamin D Binding Protein in Health and Disease 3.0)
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Open AccessArticle
The Role of Collagen VIII in the Aging Mouse Kidney
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Ngoc Dong Nhi Vo, Nikolaus Gaßler, Gunter Wolf and Ivonne Loeffler
Int. J. Mol. Sci. 2024, 25(9), 4805; https://doi.org/10.3390/ijms25094805 (registering DOI) - 28 Apr 2024
Abstract
The gradual loss of kidney function due to increasing age is accompanied by structural changes such as fibrosis of the tissue. The underlying molecular mechanisms are complex, but not yet fully understood. Non-fibrillar collagen type VIII (COL8) could be a potential factor in
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The gradual loss of kidney function due to increasing age is accompanied by structural changes such as fibrosis of the tissue. The underlying molecular mechanisms are complex, but not yet fully understood. Non-fibrillar collagen type VIII (COL8) could be a potential factor in the fibrosis processes of the aging kidney. A pathophysiological significance of COL8 has already been demonstrated in the context of diabetic kidney disease, with studies showing that it directly influences both the development and progression of renal fibrosis occurring. The aim of this study was to investigate whether COL8 impacts age-related micro-anatomical and functional changes in a mouse model. The kidneys of wild-type (Col8-wt) and COL8-knockout (Col8-ko) mice of different age and sex were characterized with regard to the expression of molecular fibrosis markers, the development of nephrosclerosis and renal function. The age-dependent regulation of COL8 mRNA expression in the wild-type revealed sex-dependent effects that were not observed with collagen IV (COL4). Histochemical staining and protein analysis of profibrotic cytokines TGF-β1 (transforming growth factor) and CTGF (connective tissue growth factor) in mouse kidneys showed significant age effects as well as interactions of the factors age, sex and Col8 genotype. There were also significant age and Col8 genotype effects in the renal function data analyzed by urinary cystatin C. In summary, the present study shows, for the first time, that COL8 is regulated in an age- and sex-dependent manner in the mouse kidney and that the expression of COL8 influences the severity of age-induced renal fibrosis and function.
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(This article belongs to the Special Issue Aging and Chronic Kidney Disease)
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Molecular Design Using Selected Concentration Effects in Optically Activated Fluorescent Matrices
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Aneta Lewkowicz, Katarzyna Walczewska-Szewc, Martyna Czarnomska, Emilia Gruszczyńska, Mattia Pierpaoli, Robert Bogdanowicz and Zygmunt Gryczyński
Int. J. Mol. Sci. 2024, 25(9), 4804; https://doi.org/10.3390/ijms25094804 (registering DOI) - 28 Apr 2024
Abstract
Molecular physics plays a pivotal role in various fields, including medicine, pharmaceuticals, and broader industrial applications. This study aims to enhance the methods for producing specific optically active materials with distinct spectroscopic properties at the molecular level, which are crucial for these sectors,
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Molecular physics plays a pivotal role in various fields, including medicine, pharmaceuticals, and broader industrial applications. This study aims to enhance the methods for producing specific optically active materials with distinct spectroscopic properties at the molecular level, which are crucial for these sectors, while prioritizing human safety in both production and application. Forensic science, a significant socio-economic field, often employs hazardous substances in analyzing friction ridges on porous surfaces, posing safety concerns. In response, we formulated novel, non-toxic procedures for examining paper evidence, particularly thermal papers. Our laboratory model utilizes a polyvinyl alcohol polymer as a rigid matrix to emulate the thermal paper’s environment, enabling precise control over the spectroscopic characteristics of 1,8-diazafluoro-9-one (DFO). We identified and analyzed the cyclodimer 1,8-diazafluoren-9-one (DAK DFO), which is a non-toxic and biocompatible alternative for revealing forensic marks. The reagents used to preserve fingerprints were optimized for their effectiveness and stability. Using stationary absorption and emission spectroscopy, along with time-resolved emission studies, we verified the spectroscopic attributes of the new structures under deliberate aggregation conditions. Raman spectroscopy and quantum mechanical computations substantiated the cyclodimer’s configuration. The investigation provides robust scientific endorsement for the novel compound and its structural diversity, influenced by the solvatochromic sensitivity of the DFO precursor. Our approach to monitoring aggregation processes signifies a substantial shift in synthetic research paradigms, leveraging simple chemistry to yield an innovative contribution to forensic science methodologies.
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(This article belongs to the Special Issue Functional Polymeric Materials: From Synthesis to Applications)
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DeepSub: Utilizing Deep Learning for Predicting the Number of Subunits in Homo-Oligomeric Protein Complexes
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Rui Deng, Ke Wu, Jiawei Lin, Dehang Wang, Yuanyuan Huang, Yang Li, Zhenkun Shi, Zihan Zhang, Zhiwen Wang, Zhitao Mao, Xiaoping Liao and Hongwu Ma
Int. J. Mol. Sci. 2024, 25(9), 4803; https://doi.org/10.3390/ijms25094803 (registering DOI) - 28 Apr 2024
Abstract
The molecular weight (MW) of an enzyme is a critical parameter in enzyme-constrained models (ecModels). It is determined by two factors: the presence of subunits and the abundance of each subunit. Although the number of subunits (NS) can potentially be obtained from UniProt,
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The molecular weight (MW) of an enzyme is a critical parameter in enzyme-constrained models (ecModels). It is determined by two factors: the presence of subunits and the abundance of each subunit. Although the number of subunits (NS) can potentially be obtained from UniProt, this information is not readily available for most proteins. In this study, we addressed this gap by extracting and curating subunit information from the UniProt database to establish a robust benchmark dataset. Subsequently, we propose a novel model named DeepSub, which leverages the protein language model and Bi-directional Gated Recurrent Unit (GRU), to predict NS in homo-oligomers solely based on protein sequences. DeepSub demonstrates remarkable accuracy, achieving an accuracy rate as high as 0.967, surpassing the performance of QUEEN. To validate the effectiveness of DeepSub, we performed predictions for protein homo-oligomers that have been reported in the literature but are not documented in the UniProt database. Examples include homoserine dehydrogenase from Corynebacterium glutamicum, Matrilin-4 from Mus musculus and Homo sapiens, and the Multimerins protein family from M. musculus and H. sapiens. The predicted results align closely with the reported findings in the literature, underscoring the reliability and utility of DeepSub.
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(This article belongs to the Special Issue Deep Learning for Modeling the Structure, Dynamics, and Function of Small and Large Molecules)
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Immune Dysregulation in Endometriomas: Implications for Inflammation
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Izabela Dymanowska-Dyjak, Barbara Terpiłowska, Izabela Morawska-Michalska, Adam Michalski, Grzegorz Polak, Michał Terpiłowski, Mansur Rahnama-Hezavah and Ewelina Grywalska
Int. J. Mol. Sci. 2024, 25(9), 4802; https://doi.org/10.3390/ijms25094802 (registering DOI) - 28 Apr 2024
Abstract
The most common manifestation of endometriosis, a condition characterized by the presence of endometrial-like tissue outside of the uterus, is the endometrioma, a cystic ovarian lesion. It is a commonly occurring condition associated with chronic pelvic pain exacerbated prior to and during menstruation,
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The most common manifestation of endometriosis, a condition characterized by the presence of endometrial-like tissue outside of the uterus, is the endometrioma, a cystic ovarian lesion. It is a commonly occurring condition associated with chronic pelvic pain exacerbated prior to and during menstruation, as well as infertility. The exact pathomechanisms of the endometrioma are still not fully understood. Emerging evidence suggests a pivotal role of immune dysregulation in the pathogenesis of endometriomas, primarily influencing both local and systemic inflammatory processes. Among the factors implicated in the creation of the inflammatory milieu associated with endometriomas, alterations in both serum and local levels of several cytokines stand out, including IL-6, IL-8, and IL-1β, along with abnormalities in the innate immune system. While numerous signaling pathways have been suggested to play a role in the inflammatory process linked to endometriomas, only NF-κB has been conclusively demonstrated to be involved. Additionally, increased oxidative stress, both resulting from and contributing to endometriomas, has been identified as a primary driver of both systemic and local inflammation associated with the condition. This article reviews the current understanding of immune dysfunctions in the endometrioma and their implications for inflammation.
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(This article belongs to the Special Issue Endometriosis: From Molecular Basis to Therapy)
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The Role of Structural Variants in the Genetic Architecture of Parkinson’s Disease
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Abigail Miano-Burkhardt, Pilar Alvarez Jerez, Kensuke Daida, Sara Bandres Ciga and Kimberley J. Billingsley
Int. J. Mol. Sci. 2024, 25(9), 4801; https://doi.org/10.3390/ijms25094801 (registering DOI) - 27 Apr 2024
Abstract
Parkinson’s disease (PD) significantly impacts millions of individuals worldwide. Although our understanding of the genetic foundations of PD has advanced, a substantial portion of the genetic variation contributing to disease risk remains unknown. Current PD genetic studies have primarily focused on one form
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Parkinson’s disease (PD) significantly impacts millions of individuals worldwide. Although our understanding of the genetic foundations of PD has advanced, a substantial portion of the genetic variation contributing to disease risk remains unknown. Current PD genetic studies have primarily focused on one form of genetic variation, single nucleotide variants (SNVs), while other important forms of genetic variation, such as structural variants (SVs), are mostly ignored due to the complexity of detecting these variants with traditional sequencing methods. Yet, these forms of genetic variation play crucial roles in gene expression and regulation in the human brain and are causative of numerous neurological disorders, including forms of PD. This review aims to provide a comprehensive overview of our current understanding of the involvement of coding and noncoding SVs in the genetic architecture of PD.
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(This article belongs to the Special Issue Understanding the Role of Non-coding DNA in Neurodegenerative Disease)
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Platelet Biorheology and Mechanobiology in Thrombosis and Hemostasis: Perspectives from Multiscale Computation
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Rukiye Tuna, Wenjuan Yi, Esmeralda Crespo Cruz, JP Romero, Yi Ren, Jingjiao Guan, Yan Li, Yuefan Deng, Danny Bluestein, Zixiang Leonardo Liu and Jawaad Sheriff
Int. J. Mol. Sci. 2024, 25(9), 4800; https://doi.org/10.3390/ijms25094800 (registering DOI) - 27 Apr 2024
Abstract
Thrombosis is the pathological clot formation under abnormal hemodynamic conditions, which can result in vascular obstruction, causing ischemic strokes and myocardial infarction. Thrombus growth under moderate to low shear (<1000 s ) relies on platelet activation and coagulation. Thrombosis at elevated
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Thrombosis is the pathological clot formation under abnormal hemodynamic conditions, which can result in vascular obstruction, causing ischemic strokes and myocardial infarction. Thrombus growth under moderate to low shear (<1000 s ) relies on platelet activation and coagulation. Thrombosis at elevated high shear rates (>10,000 s ) is predominantly driven by unactivated platelet binding and aggregating mediated by von Willebrand factor (VWF), while platelet activation and coagulation are secondary in supporting and reinforcing the thrombus. Given the molecular and cellular level information it can access, multiscale computational modeling informed by biology can provide new pathophysiological mechanisms that are otherwise not accessible experimentally, holding promise for novel first-principle-based therapeutics. In this review, we summarize the key aspects of platelet biorheology and mechanobiology, focusing on the molecular and cellular scale events and how they build up to thrombosis through platelet adhesion and aggregation in the presence or absence of platelet activation. In particular, we highlight recent advancements in multiscale modeling of platelet biorheology and mechanobiology and how they can lead to the better prediction and quantification of thrombus formation, exemplifying the exciting paradigm of digital medicine.
Full article
(This article belongs to the Special Issue The Role of Platelets in Development and Disease: Thrombosis across the Lifespan)
Open AccessArticle
Hydroxytyrosol, a Promising Supplement in the Management of Human Stroke: An Exploratory Study
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Ángela Naranjo, Mª Josefa Álvarez-Soria, Pilar Aranda-Villalobos, Ana Mª Martínez-Rodríguez, Esther Martínez-Lara and Eva Siles
Int. J. Mol. Sci. 2024, 25(9), 4799; https://doi.org/10.3390/ijms25094799 (registering DOI) - 27 Apr 2024
Abstract
Hydroxytyrosol (HT) is a bioactive olive oil phenol with beneficial effects in a number of pathological situations. We have previously demonstrated that an HT-enriched diet could serve as a beneficial therapeutic approach to attenuate ischemic-stroke-associated damage in mice. Our exploratory pilot study examined
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Hydroxytyrosol (HT) is a bioactive olive oil phenol with beneficial effects in a number of pathological situations. We have previously demonstrated that an HT-enriched diet could serve as a beneficial therapeutic approach to attenuate ischemic-stroke-associated damage in mice. Our exploratory pilot study examined this effect in humans. Particularly, a nutritional supplement containing 15 mg of HT/day was administered to patients 24 h after the onset of stroke, for 45 days. Biochemical and oxidative-stress-related parameters, blood pressure levels, serum proteome, and neurological and functional outcomes were evaluated at 45 and 90 days and compared to a control group. The main findings were that the daily administration of HT after stroke could: (i) favor the decrease in the percentage of glycated hemoglobin and diastolic blood pressure, (ii) control the increase in nitric oxide and exert a plausible protective effect in oxidative stress, (iii) modulate the evolution of the serum proteome and, particularly, the expression of apolipoproteins, and (iv) be beneficial for certain neurological and functional outcomes. Although a larger trial is necessary, this study suggests that HT could be a beneficial nutritional complement in the management of human stroke.
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(This article belongs to the Special Issue Health Promoting Benefits of Natural Products and Functional Foods)
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Potential Involvement of the South American Lungfish Intelectin-2 in Innate-Associated Immune Modulation
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Gabriela Patrícia Martins de Almeida Bernardes, Gustavo Marques Serra, Lucas da Silva e Silva, Maíra Pompeu Martins, Louise Neiva Perez, Fábio Alberto de Molfetta, Agenor Valadares Santos and Maria Paula Cruz Schneider
Int. J. Mol. Sci. 2024, 25(9), 4798; https://doi.org/10.3390/ijms25094798 (registering DOI) - 27 Apr 2024
Abstract
Intelectins belong to a family of lectins with specific and transitory carbohydrate interaction capabilities. These interactions are related to the activity of agglutinating pathogens, as intelectins play a significant role in immunity. Despite the prominent immune defense function of intelectins, limited information about
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Intelectins belong to a family of lectins with specific and transitory carbohydrate interaction capabilities. These interactions are related to the activity of agglutinating pathogens, as intelectins play a significant role in immunity. Despite the prominent immune defense function of intelectins, limited information about its structural characteristics and carbohydrate interaction properties is available. This study investigated an intelectin transcript identified in RNA-seq data obtained from the South American lungfish (Lepidosiren paradoxa), namely LpITLN2-B. The structural analyses predicted LpITLN2-B to be a homo-trimeric globular protein with the fibrinogen-like functional domain (FReD), exhibiting a molecular mass of 57 kDa. The quaternary structure is subdivided into three monomers, A, B, and C, and each domain comprises 11 β-sheets: an anti-parallel β-sheet, a β-hairpin, and a disordered β-sheet structure. Molecular docking demonstrates a significant interaction with disaccharides rather than monosaccharides. The preferential interaction with disaccharides highlights the potential interaction with pathogen molecules, such as LPS and Poly(I:C). The hemagglutination assay inhibited lectins activity, especially maltose and sucrose, highlighting lectin activity in L. paradoxa samples. Overall, our results show the potential relevance of LpITLN2-B in L. paradoxa immune defense against pathogens.
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(This article belongs to the Special Issue Fish Immunology 4.0)
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In Vitro Evaluation of Phytobiotic Mixture Antibacterial Potential against Enterococcus spp. Strains Isolated from Broiler Chicken
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Karolina Wódz, Karolina A. Chodkowska, Hubert Iwiński, Henryk Różański and Jakub Wojciechowski
Int. J. Mol. Sci. 2024, 25(9), 4797; https://doi.org/10.3390/ijms25094797 (registering DOI) - 27 Apr 2024
Abstract
Enterococcus spp. are normal intestinal tract microflorae found in poultry. However, the last decades have shown that several species, e.g., Enterococcus cecorum, have become emerging pathogens in broilers and may cause numerous losses in flocks. In this study, two combinations (H1 and
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Enterococcus spp. are normal intestinal tract microflorae found in poultry. However, the last decades have shown that several species, e.g., Enterococcus cecorum, have become emerging pathogens in broilers and may cause numerous losses in flocks. In this study, two combinations (H1 and H2) of menthol, 1,8-cineol, linalool, methyl salicylate, γ-terpinene, p-cymene, trans-anethole, terpinen-4-ol and thymol were used in an in vitro model, analyzing its effectiveness against the strains E. cecorum, E. faecalis, E. faecium, E. hirae and E. gallinarum isolated from broiler chickens from industrial farms. To identify the isolated strains classical microbiological methods and VITEK 2 GP cards were used. Moreover for E. cecorum a PCR test was used.. Antibiotic sensitivity (MIC) tests were performed for all the strains. For the composition H1, the effective dilution for E. cecorum and E. hirae strains was 1:512, and for E. faecalis, E. faecium and E. gallinarum, 1:1024. The second mixture (H2) showed very similar results with an effectiveness at 1:512 for E. cecorum and E. hirae and 1:1024 for E. faecalis, E. faecium and E. gallinarum. The presented results suggest that the proposed composition is effective against selected strains of Enterococcus in an in vitro model, and its effect is comparable to classical antibiotics used to treat this pathogen in poultry. This may suggest that this product may also be effective in vivo and provide effective support in the management of enterococcosis in broiler chickens.
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(This article belongs to the Special Issue Recent Research on Antimicrobial Agents)
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Estrogen-Related Receptor α: A Key Transcription Factor in the Regulation of Energy Metabolism at an Organismic Level and a Target of the ABA/LANCL Hormone Receptor System
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Sonia Spinelli, Maurizio Bruschi, Mario Passalacqua, Lucrezia Guida, Mirko Magnone, Laura Sturla and Elena Zocchi
Int. J. Mol. Sci. 2024, 25(9), 4796; https://doi.org/10.3390/ijms25094796 (registering DOI) - 27 Apr 2024
Abstract
The orphan nuclear receptor ERRα is the most extensively researched member of the estrogen-related receptor family and holds a pivotal role in various functions associated with energy metabolism, especially in tissues characterized by high energy requirements, such as the heart, skeletal muscle, adipose
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The orphan nuclear receptor ERRα is the most extensively researched member of the estrogen-related receptor family and holds a pivotal role in various functions associated with energy metabolism, especially in tissues characterized by high energy requirements, such as the heart, skeletal muscle, adipose tissue, kidney, and brain. Abscisic acid (ABA), traditionally acknowledged as a plant stress hormone, is detected and actively functions in organisms beyond the land plant kingdom, encompassing cyanobacteria, fungi, algae, protozoan parasites, lower Metazoa, and mammals. Its ancient, cross-kingdom role enables ABA and its signaling pathway to regulate cell responses to environmental stimuli in various organisms, such as marine sponges, higher plants, and humans. Recent advancements in understanding the physiological function of ABA and its mammalian receptors in governing energy metabolism and mitochondrial function in myocytes, adipocytes, and neuronal cells suggest potential therapeutic applications for ABA in pre-diabetes, diabetes, and cardio-/neuroprotection. The ABA/LANCL1-2 hormone/receptor system emerges as a novel regulator of ERRα expression levels and transcriptional activity, mediated through the AMPK/SIRT1/PGC-1α axis. There exists a reciprocal feed-forward transcriptional relationship between the LANCL proteins and transcriptional coactivators ERRα/PGC-1α, which may be leveraged using natural or synthetic LANCL agonists to enhance mitochondrial function across various clinical contexts.
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(This article belongs to the Special Issue Hormone/Receptor System in Human Diseases)
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EGCG Disrupts the LIN28B/Let-7 Interaction and Reduces Neuroblastoma Aggressiveness
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Simona Cocchi, Valentina Greco, Viktoryia Sidarovich, Jacopo Vigna, Francesca Broso, Diana Corallo, Jacopo Zasso, Angela Re, Emanuele Filiberto Rosatti, Sara Longhi, Andrea Defant, Federico Ladu, Vanna Sanna, Valentina Adami, Vito G. D’Agostino, Mattia Sturlese, Mario Sechi, Sanja Aveic, Ines Mancini, Denise Sighel and Alessandro Quattroneadd
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Int. J. Mol. Sci. 2024, 25(9), 4795; https://doi.org/10.3390/ijms25094795 (registering DOI) - 27 Apr 2024
Abstract
Neuroblastoma (NB) is the most commonly diagnosed extracranial solid tumor in children, accounting for 15% of all childhood cancer deaths. Although the 5-year survival rate of patients with a high-risk disease has increased in recent decades, NB remains a challenge in pediatric oncology,
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Neuroblastoma (NB) is the most commonly diagnosed extracranial solid tumor in children, accounting for 15% of all childhood cancer deaths. Although the 5-year survival rate of patients with a high-risk disease has increased in recent decades, NB remains a challenge in pediatric oncology, and the identification of novel potential therapeutic targets and agents is an urgent clinical need. The RNA-binding protein LIN28B has been identified as an oncogene in NB and is associated with a poor prognosis. Given that LIN28B acts by negatively regulating the biogenesis of the tumor suppressor let-7 miRNAs, we reasoned that selective interference with the LIN28B/let-7 miRNA interaction would increase let-7 miRNA levels, ultimately leading to reduced NB aggressiveness. Here, we selected (−)-epigallocatechin 3-gallate (EGCG) out of 4959 molecules screened as the molecule with the best inhibitory activity on LIN28B/let-7 miRNA interaction and showed that treatment with PLC/PLGA-PEG nanoparticles containing EGCG (EGCG-NPs) led to an increase in mature let-7 miRNAs and a consequent inhibition of NB cell growth. In addition, EGCG-NP pretreatment reduced the tumorigenic potential of NB cells in vivo. These experiments suggest that the LIN28B/let-7 miRNA axis is a good therapeutic target in NB and that EGCG, which can interfere with this interaction, deserves further preclinical evaluation.
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(This article belongs to the Special Issue Exploring Novel Molecular, Metabolic and Cellular Mechanisms for Developing New Therapeutic Targets against Childhood Cancers)
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Light Supplementation in Pitaya Orchards Induces Pitaya Flowering in Winter by Promoting Phytohormone Biosynthesis
by
Meng Wang, Jiaxue Li, Tao Li, Shaoling Kang, Senrong Jiang, Jiaquan Huang and Hua Tang
Int. J. Mol. Sci. 2024, 25(9), 4794; https://doi.org/10.3390/ijms25094794 (registering DOI) - 27 Apr 2024
Abstract
The interaction between light and phytohormones is crucial for plant growth and development. The practice of supplementing light at night during winter to promote pitaya flowering and thereby enhance yield has been shown to be crucial and widely used. However, it remains unclear
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The interaction between light and phytohormones is crucial for plant growth and development. The practice of supplementing light at night during winter to promote pitaya flowering and thereby enhance yield has been shown to be crucial and widely used. However, it remains unclear how supplemental winter light regulates phytohormone levels to promote flowering in pitaya. In this study, through analyzing the transcriptome data of pitaya at four different stages (NL, L0, L1, L2), we observed that differentially expressed genes (DEGs) were mainly enriched in the phytohormone biosynthesis pathway. We further analyzed the data and found that cytokinin (CK) content first increased at the L0 stage and then decreased at the L1 and L2 stages after supplemental light treatment compared to the control (NL). Gibberellin (GA), auxin (IAA), salicylic acid (SA), and jasmonic acid (JA) content increased during the formation of flower buds (L1, L2 stages). In addition, the levels of GA, ethylene (ETH), IAA, and abscisic acid (ABA) increased in flower buds after one week of development (L2f). Our results suggest that winter nighttime supplemental light can interact with endogenous hormone signaling in pitaya, particularly CK, to regulate flower bud formation. These results contribute to a better understanding of the mechanism of phytohormone interactions during the induction of flowering in pitaya under supplemental light in winter.
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(This article belongs to the Section Molecular Plant Sciences)
Open AccessArticle
Fetal Kidney Grafts and Organoids from Microminiature Pigs: Establishing a Protocol for Production and Long-Term Cryopreservation
by
Yuka Inage, Koki Fujimori, Masaki Takasu, Kenji Matsui, Yoshitaka Kinoshita, Keita Morimoto, Nagisa Koda, Shutaro Yamamoto, Kentaro Shimada, Takashi Yokoo and Eiji Kobayashi
Int. J. Mol. Sci. 2024, 25(9), 4793; https://doi.org/10.3390/ijms25094793 (registering DOI) - 27 Apr 2024
Abstract
Fetal organs and organoids are important tools for studying organ development. Recently, porcine organs have garnered attention as potential organs for xenotransplantation because of their high degree of similarity to human organs. However, to meet the prompt demand for porcine fetal organs by
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Fetal organs and organoids are important tools for studying organ development. Recently, porcine organs have garnered attention as potential organs for xenotransplantation because of their high degree of similarity to human organs. However, to meet the prompt demand for porcine fetal organs by patients and researchers, effective methods for producing, retrieving, and cryopreserving pig fetuses are indispensable. Therefore, in this study, to collect fetuses for kidney extraction, we employed cesarean sections to preserve the survival and fertility of the mother pig and a method for storing fetal kidneys by long-term cryopreservation. Subsequently, we evaluated the utility of these two methods. We confirmed that the kidneys of pig fetuses retrieved by cesarean section that were cryopreserved for an extended period could resume renal growth when grafted into mice and were capable of forming renal organoids. These results demonstrate the usefulness of long-term cryopreserved fetal pig organs and strongly suggest the effectiveness of our comprehensive system of pig fetus retrieval and fetal organ preservation, thereby highlighting its potential as an accelerator of xenotransplantation research and clinical innovation.
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(This article belongs to the Special Issue Recent Research in Stem Cells to Organoids)
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Pulmonary Hypertension in Sickle Cell Disease: Novel Findings of Gene Polymorphisms Related to Pathophysiology
by
Sevastianos Chatzidavid, Pagona Flevari, Ioanna Tombrou, Georgios Anastasiadis and Maria Dimopoulou On behalf of the International Hemoglobinopathy Research Network (INHERENT)
Int. J. Mol. Sci. 2024, 25(9), 4792; https://doi.org/10.3390/ijms25094792 (registering DOI) - 27 Apr 2024
Abstract
Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD), affecting 6–10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of this disease. However, questions remain, particularly regarding the clinical heterogeneity
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Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD), affecting 6–10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of this disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is currently focused on the potential role of genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the transforming growth factor-beta (TGF-β) pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future, as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield reliable results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. This review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.
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(This article belongs to the Special Issue Genetic Modifiers of Hemoglobinopathies: Recent Advances and Future Directions)
Open AccessArticle
Development, High-Throughput Profiling, and Biopanning of a Large Phage Display Single-Domain Antibody Library
by
Hee Eon Lee, Ah Hyun Cho, Jae Hyeon Hwang, Ji Woong Kim, Ha Rim Yang, Taehoon Ryu, Yushin Jung and Sukmook Lee
Int. J. Mol. Sci. 2024, 25(9), 4791; https://doi.org/10.3390/ijms25094791 (registering DOI) - 27 Apr 2024
Abstract
Immunoglobulin G-based monoclonal antibodies (mAbs) have been effective in treating various diseases, but their large molecular size can limit their penetration of tissue and efficacy in multifactorial diseases, necessitating the exploration of alternative forms. In this study, we constructed a phage display library
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Immunoglobulin G-based monoclonal antibodies (mAbs) have been effective in treating various diseases, but their large molecular size can limit their penetration of tissue and efficacy in multifactorial diseases, necessitating the exploration of alternative forms. In this study, we constructed a phage display library comprising single-domain antibodies (sdAbs; or “VHHs”), known for their small size and remarkable stability, using a total of 1.6 × 109 lymphocytes collected from 20 different alpacas, resulting in approximately 7.16 × 1010 colonies. To assess the quality of the constructed library, next-generation sequencing-based high-throughput profiling was performed, analyzing approximately 5.65 × 106 full-length VHH sequences, revealing 92% uniqueness and confirming the library’s diverse composition. Systematic characterization of the library revealed multiple sdAbs with high affinity for three therapeutically relevant antigens. In conclusion, our alpaca sdAb phage display library provides a versatile resource for diagnostics and therapeutics. Furthermore, the library’s vast natural VHH antibody repertoire offers insights for generating humanized synthetic sdAb libraries, further advancing sdAb-based therapeutics.
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(This article belongs to the Special Issue Application of High-Throughput Omics Sequencing in Personalized Medicine)
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Open AccessArticle
Design of Mixed Medicinal Plants, Rich in Polyphenols, Vitamin B2, and Palmitoylethanolamide-Based Supplement to Help Reduce Nerve Pain: A Preclinical Study
by
Simone Mulè, Giorgia Rosso, Mattia Botta, Arianna Brovero, Sara Ferrari, Rebecca Galla, Claudio Molinari and Francesca Uberti
Int. J. Mol. Sci. 2024, 25(9), 4790; https://doi.org/10.3390/ijms25094790 (registering DOI) - 27 Apr 2024
Abstract
Neuropathy affects 7–10% of the general population and is caused by a lesion or disease of the somatosensory system. The limitations of current therapies highlight the necessity of a new innovative approach to treating neuropathic pain (NP) based on the close correlation between
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Neuropathy affects 7–10% of the general population and is caused by a lesion or disease of the somatosensory system. The limitations of current therapies highlight the necessity of a new innovative approach to treating neuropathic pain (NP) based on the close correlation between oxidative stress, inflammatory process, and antioxidant action. The advantageous outcomes of a novel combination composed of Hop extract, Propolis, Ginkgo Biloba, Vitamin B, and palmitoylethanolamide (PEA) used as a treatment was evaluated in this study. To assess the absorption and biodistribution of the combination, its bioavailability was first examined in a 3D intestinal barrier model that replicated intestinal absorption. Further, a 3D nerve tissue model was developed to study the biological impacts of the combination during the essential pathways involved in NP. Our findings show that the combination could cross the intestinal barrier and reach the peripheral nervous system, where it modulates the oxidative stress, inflammation levels, and myelination mechanism (increased NRG, MPZ, ERB, and p75 levels) under Schwann cells damaging. This study proves the effectiveness of Ginkgo Biloba, Propolis, Hop extract, Vitamin B, and PEA in avoiding nerve damage and suggests a potential alternative nutraceutical treatment for NP and neuropathies.
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(This article belongs to the Collection Feature Papers in Bioactives and Nutraceuticals)
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