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
SGLT2 Inhibitors in Kidney Diseases—A Narrative Review
Int. J. Mol. Sci. 2024, 25(9), 4959; https://doi.org/10.3390/ijms25094959 (registering DOI) - 01 May 2024
Abstract
Some of the most common conditions affecting people are kidney diseases. Among them, we distinguish chronic kidney disease and acute kidney injury. Both entities pose serious health risks, so new drugs are still being sought to treat and prevent them. In recent years,
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Some of the most common conditions affecting people are kidney diseases. Among them, we distinguish chronic kidney disease and acute kidney injury. Both entities pose serious health risks, so new drugs are still being sought to treat and prevent them. In recent years, such a role has begun to be assigned to sodium-glucose cotransporter-2 (SGLT2) inhibitors. They increase the amount of glucose excreted in the urine. For this reason, they are currently used as a first-line drug in type 2 diabetes mellitus. Due to their demonstrated cardioprotective effect, they are also used in heart failure treatment. As for the renal effects of SGLT2 inhibitors, they reduce intraglomerular pressure and decrease albuminuria. This results in a slower decline in glomelular filtration rate (GFR) in patients with kidney disease. In addition, these drugs have anti-inflammatory and antifibrotic effects. In the following article, we review the evidence for the effectiveness of this group of drugs in kidney disease and their nephroprotective effect. Further research is still needed, but meta-analyses indicate SGLT2 inhibitors' efficacy in kidney disease, especially the one caused by diabetes. Development of new drugs and clinical trials on specific patient subgroups will further refine their nephroprotective effects.
Full article
(This article belongs to the Special Issue New Insights into Kidney Diseases)
Open AccessReview
Use of Statins in Heart Failure with Preserved Ejection Fraction: Current Evidence and Perspectives
by
Artem Ovchinnikov, Alexandra Potekhina, Tatiana Arefieva, Anastasiia Filatova, Fail Ageev and Evgeny Belyavskiy
Int. J. Mol. Sci. 2024, 25(9), 4958; https://doi.org/10.3390/ijms25094958 (registering DOI) - 01 May 2024
Abstract
Systemic inflammation and coronary microvascular endothelial dysfunction are essential pathophysiological factors in heart failure (HF) with preserved ejection fraction (HFpEF) that support the use of statins. The pleiotropic properties of statins, such as anti-inflammatory, antihypertrophic, antifibrotic, and antioxidant effects, are generally accepted and
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Systemic inflammation and coronary microvascular endothelial dysfunction are essential pathophysiological factors in heart failure (HF) with preserved ejection fraction (HFpEF) that support the use of statins. The pleiotropic properties of statins, such as anti-inflammatory, antihypertrophic, antifibrotic, and antioxidant effects, are generally accepted and may be beneficial in HF, especially in HFpEF. Numerous observational clinical trials have consistently shown a beneficial prognostic effect of statins in patients with HFpEF, while the results of two larger trials in patients with HFrEF have been controversial. Such differences may be related to a more pronounced impact of the pleiotropic properties of statins on the pathophysiology of HFpEF and pro-inflammatory comorbidities (arterial hypertension, diabetes mellitus, obesity, chronic kidney disease) that are more common in HFpEF. This review discusses the potential mechanisms of statin action that may be beneficial for patients with HFpEF, as well as clinical trials that have evaluated the statin effects on left ventricular diastolic function and clinical outcomes in patients with HFpEF.
Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Molecular Mechanisms and Potential Therapy)
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Open AccessArticle
The ZmbHLH47-ZmSnRK2.9 Module Promotes Drought Tolerance in Maize
by
Zhenwei Yan, Fajun Zhang, Chunhua Mu, Changle Ma, Guoqi Yao, Yue Sun, Jing Hou, Bingying Leng and Xia Liu
Int. J. Mol. Sci. 2024, 25(9), 4957; https://doi.org/10.3390/ijms25094957 (registering DOI) - 01 May 2024
Abstract
Drought stress globally poses a significant threat to maize (Zea mays L.) productivity and the underlying molecular mechanisms of drought tolerance remain elusive. In this study, we characterized ZmbHLH47, a basic helix–loop–helix (bHLH) transcription factor, as a positive regulator of drought tolerance
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Drought stress globally poses a significant threat to maize (Zea mays L.) productivity and the underlying molecular mechanisms of drought tolerance remain elusive. In this study, we characterized ZmbHLH47, a basic helix–loop–helix (bHLH) transcription factor, as a positive regulator of drought tolerance in maize. ZmbHLH47 expression was notably induced by both drought stress and abscisic acid (ABA). Transgenic plants overexpressing ZmbHLH47 displayed elevated drought tolerance and ABA responsiveness, while the zmbhlh47 mutant exhibited increased drought sensitivity and reduced ABA sensitivity. Mechanistically, it was revealed that ZmbHLH47 could directly bind to the promoter of ZmSnRK2.9 gene, a member of the subgroup III SnRK2 kinases, activating its expression. Furthermore, ZmSnRK2.9-overexpressing plants exhibited enhanced ABA sensitivity and drought tolerance, whereas the zmsnrk2.9 mutant displayed a decreased sensitivity to both. Notably, overexpressing ZmbHLH47 in the zmsnrk2.9 mutant closely resembled the zmsnrk2.9 mutant, indicating the importance of the ZmbHLH47-ZmSnRK2.9 module in ABA response and drought tolerance. These findings provided valuable insights and a potential genetic resource for enhancing the environmental adaptability of maize.
Full article
(This article belongs to the Special Issue Advance in Plant Abiotic Stress)
Open AccessReview
How We Interpret Thrombosis with Thrombocytopenia Syndrome?
by
Shinya Yamada and Hidesaku Asakura
Int. J. Mol. Sci. 2024, 25(9), 4956; https://doi.org/10.3390/ijms25094956 (registering DOI) - 01 May 2024
Abstract
Platelets play an important role in hemostasis, and a low platelet count usually increases the risk of bleeding. Conditions in which thrombosis occurs despite low platelet counts are referred to as thrombosis with thrombocytopenia syndrome, including heparin-induced thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia, paroxysmal
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Platelets play an important role in hemostasis, and a low platelet count usually increases the risk of bleeding. Conditions in which thrombosis occurs despite low platelet counts are referred to as thrombosis with thrombocytopenia syndrome, including heparin-induced thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia, paroxysmal nocturnal hemoglobinuria, antiphospholipid syndrome, thrombotic microangiopathy (TMA), and disseminated intravascular coagulation. TMA includes thrombotic thrombocytopenic purpura, Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (HUS), and atypical HUS. Patients with these pathologies present with thrombosis and consumptive thrombocytopenia associated with the activation of platelets and the coagulation system. Treatment varies from disease to disease, and many diseases have direct impacts on mortality and organ prognosis if therapeutic interventions are not promptly implemented. Underlying diseases and the results of physical examinations and general laboratory tests as part of a thorough workup for patients should promptly lead to therapeutic intervention before definitive diagnosis. For some diseases, the diagnosis and initial treatment must proceed in parallel. Utilization of not only laboratory tests but also various scoring systems is important for validating therapeutic interventions based on clinical information.
Full article
(This article belongs to the Special Issue Molecular Immunology in Hematological Disorders 2.0)
Open AccessArticle
Exploring Binding Pockets in the Conformational States of the SARS-CoV-2 Spike Trimers for the Screening of Allosteric Inhibitors Using Molecular Simulations and Ensemble-Based Ligand Docking
by
Grace Gupta and Gennady Verkhivker
Int. J. Mol. Sci. 2024, 25(9), 4955; https://doi.org/10.3390/ijms25094955 (registering DOI) - 01 May 2024
Abstract
Understanding mechanisms of allosteric regulation remains elusive for the SARS-CoV-2 spike protein, despite the increasing interest and effort in discovering allosteric inhibitors of the viral activity and interactions with the host receptor ACE2. The challenges of discovering allosteric modulators of the SARS-CoV-2 spike
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Understanding mechanisms of allosteric regulation remains elusive for the SARS-CoV-2 spike protein, despite the increasing interest and effort in discovering allosteric inhibitors of the viral activity and interactions with the host receptor ACE2. The challenges of discovering allosteric modulators of the SARS-CoV-2 spike proteins are associated with the diversity of cryptic allosteric sites and complex molecular mechanisms that can be employed by allosteric ligands, including the alteration of the conformational equilibrium of spike protein and preferential stabilization of specific functional states. In the current study, we combine conformational dynamics analysis of distinct forms of the full-length spike protein trimers and machine-learning-based binding pocket detection with the ensemble-based ligand docking and binding free energy analysis to characterize the potential allosteric binding sites and determine structural and energetic determinants of allosteric inhibition for a series of experimentally validated allosteric molecules. The results demonstrate a good agreement between computational and experimental binding affinities, providing support to the predicted binding modes and suggesting key interactions formed by the allosteric ligands to elicit the experimentally observed inhibition. We establish structural and energetic determinants of allosteric binding for the experimentally known allosteric molecules, indicating a potential mechanism of allosteric modulation by targeting the hinges of the inter-protomer movements and blocking conformational changes between the closed and open spike trimer forms. The results of this study demonstrate that combining ensemble-based ligand docking with conformational states of spike protein and rigorous binding energy analysis enables robust characterization of the ligand binding modes, the identification of allosteric binding hotspots, and the prediction of binding affinities for validated allosteric modulators, which is consistent with the experimental data. This study suggested that the conformational adaptability of the protein allosteric sites and the diversity of ligand bound conformations are both in play to enable efficient targeting of allosteric binding sites and interfere with the conformational changes.
Full article
(This article belongs to the Special Issue Computational Pharmacology in Drug Discovery)
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Open AccessBrief Report
Vitamin D Attenuates Fibrotic Properties of Fibrous Dysplasia-Derived Cells for the Transit towards Osteocytic Phenotype
by
Ha-Young Kim, Jung-Hee Shim, Baek-Kyu Kim and Chan-Yeong Heo
Int. J. Mol. Sci. 2024, 25(9), 4954; https://doi.org/10.3390/ijms25094954 (registering DOI) - 01 May 2024
Abstract
Fibrous dysplasia (FD) poses a therapeutic challenge due to the dysregulated extracellular matrix (ECM) accumulation within affected bone tissues. In this study, we investigate the therapeutic potential of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in managing FD by examining its effects on
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Fibrous dysplasia (FD) poses a therapeutic challenge due to the dysregulated extracellular matrix (ECM) accumulation within affected bone tissues. In this study, we investigate the therapeutic potential of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in managing FD by examining its effects on FD-derived cells in vitro. Our findings demonstrate that 1,25(OH)2D3 treatment attenuates the pro-fibrotic phenotype of FD-derived cells by suppressing the expression of key pro-fibrotic markers and inhibiting cell proliferation and migration. Moreover, 1,25(OH)2D3 enhances mineralization by attenuating pre-osteoblastic cellular hyperactivity and promoting maturation towards an osteocytic phenotype. These results offer valuable insights into potential treatments for FD, highlighting the role of 1,25(OH)2D3 in modulating the pathological properties of FD-derived cells.
Full article
(This article belongs to the Special Issue Application of Natural Products in Prevention of Bone Related Diseases)
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Open AccessArticle
DDX18 Facilitates the Tumorigenesis of Lung Adenocarcinoma by Promoting Cell Cycle Progression through the Upregulation of CDK4
by
Bingbing Feng, Xinying Wang, Ding Qiu, Haiyang Sun, Jianping Deng, Ying Tan, Kaile Ji, Shaoting Xu, Shuishen Zhang and Ce Tang
Int. J. Mol. Sci. 2024, 25(9), 4953; https://doi.org/10.3390/ijms25094953 (registering DOI) - 01 May 2024
Abstract
Lung adenocarcinoma (LUAD) is the most prevalent and aggressive subtype of lung cancer, exhibiting a dismal prognosis with a five-year survival rate below 5%. DEAD-box RNA helicase 18 (DDX18, gene symbol DDX18), a crucial regulator of RNA metabolism, has been
[...] Read more.
Lung adenocarcinoma (LUAD) is the most prevalent and aggressive subtype of lung cancer, exhibiting a dismal prognosis with a five-year survival rate below 5%. DEAD-box RNA helicase 18 (DDX18, gene symbol DDX18), a crucial regulator of RNA metabolism, has been implicated in various cellular processes, including cell cycle control and tumorigenesis. However, its role in LUAD pathogenesis remains elusive. This study demonstrates the significant upregulation of DDX18 in LUAD tissues and its association with poor patient survival (from public databases). Functional in vivo and in vitro assays revealed that DDX18 knockdown potently suppresses LUAD progression. RNA sequencing and chromatin immunoprecipitation experiments identified cyclin-dependent kinase 4 (CDK4), a cell cycle regulator, as a direct transcriptional target of DDX18. Notably, DDX18 depletion induced G1 cell cycle arrest, while its overexpression promoted cell cycle progression even in normal lung cells. Interestingly, while the oncogenic protein c-Myc bound to the DDX18 promoter, it did not influence its expression. Collectively, these findings establish DDX18 as a potential oncogene in LUAD, functioning through the CDK4-mediated cell cycle pathway. DDX18 may represent a promising therapeutic target for LUAD intervention.
Full article
(This article belongs to the Section Molecular Oncology)
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Open AccessEditorial
Chemistry and Biology of Noncanonical Nucleic Acid Structures: From Physicochemical Properties to Therapeutic Applications
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Jussara Amato, Antonio Randazzo and Bruno Pagano
Int. J. Mol. Sci. 2024, 25(9), 4952; https://doi.org/10.3390/ijms25094952 (registering DOI) - 01 May 2024
Abstract
The aim of this Special Issue is to highlight significant and new aspects concerning the chemistry and biology of noncanonical nucleic acid structures, with emphasis on their structure, stability, and conformational equilibria, as well as on the biological relevance of their interactions with
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The aim of this Special Issue is to highlight significant and new aspects concerning the chemistry and biology of noncanonical nucleic acid structures, with emphasis on their structure, stability, and conformational equilibria, as well as on the biological relevance of their interactions with proteins and ligands [...]
Full article
(This article belongs to the Special Issue Chemistry and Biology of Noncanonical Nucleic Acid Structures: From Physicochemical Properties to Therapeutic Applications)
Open AccessEditorial
Role of Bioactives in Neurodegenerative Diseases
by
Lefteris C. Zacharia
Int. J. Mol. Sci. 2024, 25(9), 4951; https://doi.org/10.3390/ijms25094951 (registering DOI) - 01 May 2024
Abstract
Neurodegenerative diseases (NDs) affect millions worldwide, with the two most prevalent being Alzheimer’s and Parkinson disease [...]
Full article
(This article belongs to the Special Issue Role of Bioactives in Neurodegenerative Diseases)
Open AccessCommunication
Lactate Dehydrogenase-Elevating Virus Infection Inhibits MOG Peptide Presentation by CD11b+CD11c+ Dendritic Cells in a Mouse Model of Multiple Sclerosis
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Pyone Pyone Soe, Mélanie Gaignage, Mohamed F. Mandour, Etienne Marbaix, Jacques Van Snick and Jean-Paul Coutelier
Int. J. Mol. Sci. 2024, 25(9), 4950; https://doi.org/10.3390/ijms25094950 (registering DOI) - 01 May 2024
Abstract
Infections may affect the course of autoimmune inflammatory diseases of the central nervous system (CNS), such as multiple sclerosis (MS). Infections with lactate dehydrogenase-elevating virus (LDV) protected mice from developing experimental autoimmune encephalomyelitis (EAE), a mouse counterpart of MS. Uninfected C57BL/6 mice immunized
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Infections may affect the course of autoimmune inflammatory diseases of the central nervous system (CNS), such as multiple sclerosis (MS). Infections with lactate dehydrogenase-elevating virus (LDV) protected mice from developing experimental autoimmune encephalomyelitis (EAE), a mouse counterpart of MS. Uninfected C57BL/6 mice immunized with the myelin oligodendrocyte glycoprotein peptide (MOG35–55) experienced paralysis and lost weight at a greater rate than mice who had previously been infected with LDV. LDV infection decreased the presentation of the MOG peptide by CD11b+CD11c+ dendritic cells (DC) to pathogenic T lymphocytes. When comparing non-infected mice to infected mice, the histopathological examination of the CNS showed more areas of demyelination and CD45+ and CD3+, but not Iba1+ cell infiltration. These results suggest that the protective effect of LDV infection against EAE development is mediated by a suppression of myelin antigen presentation by a specific DC subset to autoreactive T lymphocytes. Such a mechanism might contribute to the general suppressive effect of infections on autoimmune diseases known as the hygiene hypothesis.
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(This article belongs to the Special Issue Animal Research Model for Neurological Diseases)
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Open AccessArticle
Thymol, a Monoterpenoid within Polymeric Iodophor Formulations and Their Antimicrobial Activities
by
Zehra Edis and Samir Haj Bloukh
Int. J. Mol. Sci. 2024, 25(9), 4949; https://doi.org/10.3390/ijms25094949 (registering DOI) - 01 May 2024
Abstract
Antimicrobial resistance (AMR) poses an emanating threat to humanity’s future. The effectiveness of commonly used antibiotics against microbial infections is declining at an alarming rate. As a result, morbidity and mortality rates are soaring, particularly among immunocompromised populations. Exploring alternative solutions, such as
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Antimicrobial resistance (AMR) poses an emanating threat to humanity’s future. The effectiveness of commonly used antibiotics against microbial infections is declining at an alarming rate. As a result, morbidity and mortality rates are soaring, particularly among immunocompromised populations. Exploring alternative solutions, such as medicinal plants and iodine, shows promise in combating resistant pathogens. Such antimicrobials could effectively inhibit microbial proliferation through synergistic combinations. In our study, we prepared a formulation consisting of Aloe barbadensis Miller (AV), Thymol, iodine (I2), and polyvinylpyrrolidone (PVP). Various analytical methods including SEM/EDS, UV-vis, Raman, FTIR, and XRD were carried out to verify the purity, composition, and morphology of AV-PVP-Thymol-I2. We evaluated the inhibitory effects of this formulation against 10 selected reference strains using impregnated sterile discs, surgical sutures, gauze bandages, surgical face masks, and KN95 masks. The antimicrobial properties of AV-PVP-Thymol-I2 were assessed through disc diffusion methods against 10 reference strains in comparison with two common antibiotics. The 25-month-old formulation exhibited slightly lower inhibitory zones, indicating changes in the sustained-iodine-release reservoir. Our findings confirm AV-PVP-Thymol-I2 as a potent antifungal and antibacterial agent against the reference strains, demonstrating particularly strong inhibitory action on surgical sutures, cotton bandages, and face masks. These results enable the potential use of the formulation AV-PVP-Thymol-I2 as a promising antimicrobial agent against wound infections and as a spray-on contact-killing agent.
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(This article belongs to the Section Molecular Microbiology)
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Open AccessArticle
Effect of Morphology Modification of BiFeO3 on Photocatalytic Efficacy of P-g-C3N4/BiFeO3 Composites
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Abubakar Usman Katsina, Diana-Luciana Cursaru, Dănuţa Matei and Sonia Mihai
Int. J. Mol. Sci. 2024, 25(9), 4948; https://doi.org/10.3390/ijms25094948 - 01 May 2024
Abstract
This current study assessed the impacts of morphology adjustment of perovskite BiFeO3 (BFO) on the construction and photocatalytic activity of P-infused g-C3N4/U-BiFeO3 (U-BFO/PCN) heterostructured composite photocatalysts. Favorable formation of U-BFO/PCN composites was attained via urea-aided morphology-controlled hydrothermal
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This current study assessed the impacts of morphology adjustment of perovskite BiFeO3 (BFO) on the construction and photocatalytic activity of P-infused g-C3N4/U-BiFeO3 (U-BFO/PCN) heterostructured composite photocatalysts. Favorable formation of U-BFO/PCN composites was attained via urea-aided morphology-controlled hydrothermal synthesis of BFO followed by solvosonication-mediated fusion with already synthesized P-g-C3N4 to form U-BFO/PCN composites. The prepared bare and composite photocatalysts’ morphological, textural, structural, optical, and photocatalytic performance were meticulously examined through various analytical characterization techniques and photodegradation of aqueous rhodamine B (RhB). Ellipsoids and flakes morphological structures were obtained for U-BFO and BFO, and their effects on the successful fabrication of the heterojunctions were also established. The U-BFO/PCN composite exhibits 99.2% efficiency within 20 min of visible-light irradiation, surpassing BFO/PCN (88.5%), PCN (66.8%), and U-BFO (26.1%). The pseudo-first-order kinetics of U-BFO/PCN composites is 2.41 × 10−1 min−1, equivalent to 2.2 times, 57 times, and 4.3 times of BFO/PCN (1.08 × 10−1 min−1), U-BFO, (4.20 × 10−3 min−1), and PCN, (5.60 × 10−2 min−1), respectively. The recyclability test demonstrates an outstanding photostability for U-BFO/PCN after four cyclic runs. This improved photocatalytic activity exhibited by the composites can be attributed to enhanced visible-light utilization and additional accessible active sites due to surface and electronic band modification of CN via P-doping and effective charge separation achieved via successful composites formation.
Full article
(This article belongs to the Special Issue (Di)electrical and Catalytic Functionality in Advanced (Bio)materials: Synthesis and Structure–Properties Investigation)
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Open AccessBrief Report
Ethnicity-Based Variations in Focal Adhesion Kinase Signaling in Glioblastoma Gene Expression: A Study of the Puerto Rican Hispanic Population
by
Tyrel Porter, Miguel Mayol del Valle and Lilia Kucheryavykh
Int. J. Mol. Sci. 2024, 25(9), 4947; https://doi.org/10.3390/ijms25094947 - 01 May 2024
Abstract
Glioblastoma (GBM), an aggressive form of brain cancer, has a higher incidence in non-Hispanics when compared to the US Hispanic population. Using data from RT-PCR analysis of 21 GBM tissue from Hispanic patients in Puerto Rico, we identified significant correlations in the gene
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Glioblastoma (GBM), an aggressive form of brain cancer, has a higher incidence in non-Hispanics when compared to the US Hispanic population. Using data from RT-PCR analysis of 21 GBM tissue from Hispanic patients in Puerto Rico, we identified significant correlations in the gene expression of focal adhesion kinase and proline-rich tyrosine kinase (PTK2 and PTK2B) with NGFR (nerve growth factor receptor), PDGFRB (platelet-derived growth factor receptor B), EGFR (epithelial growth factor receptor), and CXCR1 (C-X-C motif chemokine receptor 1). This study further explores these correlations found in gene expression while accounting for sex and ethnicity. Statistically significant (p < 0.05) correlations with an r value > ±0.7 were subsequently contrasted with mRNA expression data acquired from cBioPortal for 323 GBM specimens. Significant correlations in Puerto Rican male patients were found between PTK2 and PTK2B, NGFR, PDGFRB, EGFR, and CXCR1, which did not arise in non-Hispanic male patient data. The data for Puerto Rican female patients showed correlations in PTK2 with PTK2B, NGFR, PDGFRB, and EGFR, all of which did not appear in the data for non-Hispanic female patients. The data acquired from cBioPortal for non-Puerto Rican Hispanic patients supported the correlations found in the Puerto Rican population for both sexes. Our findings reveal distinct correlations in gene expression patterns, particularly involving PTK2, PTK2B, NGFR, PDGFRB, and EGFR among Puerto Rican Hispanic patients when compared to non-Hispanic counterparts.
Full article
(This article belongs to the Special Issue Novel Therapeutic Targets in Cancers 3.0)
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Open AccessArticle
Real-Time Monitoring on the Chinese Giant Salamander Using RPA-LFD
by
Lanxin Ling, Linyan Liang, Huifang Wang, Xiaolong Lin and Chenhong Li
Int. J. Mol. Sci. 2024, 25(9), 4946; https://doi.org/10.3390/ijms25094946 - 01 May 2024
Abstract
The Chinese giant salamander (Andrias davidianus), listed as an endangered species under “secondary protection” in China, faces significant threats due to ecological deterioration and the expansion of human activity. Extensive field investigations are crucial to ascertain the current status in the
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The Chinese giant salamander (Andrias davidianus), listed as an endangered species under “secondary protection” in China, faces significant threats due to ecological deterioration and the expansion of human activity. Extensive field investigations are crucial to ascertain the current status in the wild and to implement effective habitat protection measures to safeguard this species and support its population development. Traditional survey methods often fall short due to the elusive nature of the A. davidianus, presenting challenges that are time-consuming and generally ineffective. To overcome these obstacles, this study developed a real-time monitoring method that uses environmental DNA (eDNA) coupled with recombinase polymerase amplification and lateral flow strip (RPA-LFD). We designed five sets of species-specific primers and probes based on mitochondrial genome sequence alignments of A. davidianus and its close relatives. Our results indicated that four of these primer/probe sets accurately identified A. davidianus, distinguishing it from other tested caudata species using both extracted DNA samples and water samples from a tank housing an individual. This method enables the specific detection of A. davidianus genomic DNA at concentrations as low as 0.1 ng/mL within 50 min, without requiring extensive laboratory equipment. Applied in a field survey across four sites in Huangshan City, Anhui Province, where A. davidianus is known to be distributed, the method successfully detected the species at three of the four sites. The development of these primer/probe sets offers a practical tool for field surveying and monitoring, facilitating efforts in population recovery and resource conservation for A. davidianus.
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(This article belongs to the Section Molecular Biology)
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Open AccessCommunication
Enhancing Therapeutic Efficacy and Safety of Immune Checkpoint Inhibition for Bladder Cancer: A Comparative Analysis of Injectable vs. Intravesical Administration
by
Pradeep Tyagi, Jason Hafron, Jonathan Kaufman and Michael Chancellor
Int. J. Mol. Sci. 2024, 25(9), 4945; https://doi.org/10.3390/ijms25094945 (registering DOI) - 01 May 2024
Abstract
Bladder cancer (BC) presents a significant global health burden, characterized by high recurrence rates post-initial treatment. Gender differences in BC prevalence and response to therapy emphasize the importance of personalized treatment strategies. While Bacillus Calmette–Guérin (BCG) remains a cornerstone of BC therapy, resistance
[...] Read more.
Bladder cancer (BC) presents a significant global health burden, characterized by high recurrence rates post-initial treatment. Gender differences in BC prevalence and response to therapy emphasize the importance of personalized treatment strategies. While Bacillus Calmette–Guérin (BCG) remains a cornerstone of BC therapy, resistance poses a challenge, necessitating alternative strategies. Immune checkpoint inhibitors (ICIs) have shown promise, yet systemic toxicity raises concern. Intravesical administration of ICIs offers a potential solution, with recent studies demonstrating the feasibility and efficacy of intravesical pembrolizumab. Although systemic toxicity remains a concern, its localized administration may mitigate adverse events. Additionally, liposomal delivery of ICIs exhibits promises in enhancing drug penetration and reducing toxicity. Novel imaging modalities compatible with Vesical Imaging-Reporting and Data System (VI-RADS) and capable of predicting high-grade bladder cancer can aid the pre-operative shared decision making of patient and surgeon. Future research should focus on refining treatment approaches, optimizing dosing regimens, and leveraging advanced imaging techniques to improve patient outcomes. In conclusion, intravesical immunotherapy presents a promising avenue for BC treatment, offering enhanced therapeutic effectiveness while minimizing systemic toxicity. Continued research efforts are essential to validate these findings and optimize intravesical immunotherapy’s role in BC management, ultimately improving patient outcomes.
Full article
(This article belongs to the Special Issue Molecular Diagnostics and Therapeutic Target in Bladder Cancer)
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Cold Atmospheric Pressure Plasma-Activated Medium Modulates Cellular Functions of Human Mesenchymal Stem/Stromal Cells In Vitro
by
Olga Hahn, Tawakalitu Okikiola Waheed, Kaarthik Sridharan, Thomas Huemerlehner, Susanne Staehlke, Mario Thürling, Lars Boeckmann, Mareike Meister, Kai Masur and Kirsten Peters
Int. J. Mol. Sci. 2024, 25(9), 4944; https://doi.org/10.3390/ijms25094944 - 01 May 2024
Abstract
Cold atmospheric pressure plasma (CAP) offers a variety of therapeutic possibilities and induces the formation of reactive chemical species associated with oxidative stress. Mesenchymal stem/stromal cells (MSCs) play a central role in tissue regeneration, partly because of their antioxidant properties and ability to
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Cold atmospheric pressure plasma (CAP) offers a variety of therapeutic possibilities and induces the formation of reactive chemical species associated with oxidative stress. Mesenchymal stem/stromal cells (MSCs) play a central role in tissue regeneration, partly because of their antioxidant properties and ability to migrate into regenerating areas. During the therapeutic application, MSCs are directly exposed to the reactive species of CAP. Therefore, the investigation of CAP-induced effects on MSCs is essential. In this study, we quantified the amount of ROS due to the CAP activation of the culture medium. In addition, cell number, metabolic activity, stress signals, and migration were analyzed after the treatment of MSCs with a CAP-activated medium. CAP-activated media induced a significant increase in ROS but did not cause cytotoxic effects on MSCs when the treatment was singular and short-term (one day). This single treatment led to increased cell migration, an essential process in wound healing. In parallel, there was an increase in various cell stress proteins, indicating an adaptation to oxidative stress. Repeated treatments with the CAP-activated medium impaired the viability of the MSCs. The results shown here provide information on the influence of treatment frequency and intensity, which could be necessary for the therapeutic application of CAP.
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(This article belongs to the Special Issue Plasma Bioscience and Medicine Molecular Research 2.0)
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Open AccessArticle
Positron Emission Tomography with [18F]ROStrace Reveals Progressive Elevations in Oxidative Stress in a Mouse Model of Alpha-Synucleinopathy
by
Evan Gallagher, Catherine Hou, Yi Zhu, Chia-Ju Hsieh, Hsiaoju Lee, Shihong Li, Kuiying Xu, Patrick Henderson, Rea Chroneos, Malkah Sheldon, Shaipreeah Riley, Kelvin C. Luk, Robert H. Mach and Meagan J. McManus
Int. J. Mol. Sci. 2024, 25(9), 4943; https://doi.org/10.3390/ijms25094943 - 01 May 2024
Abstract
The synucleinopathies are a diverse group of neurodegenerative disorders characterized by the accumulation of aggregated alpha-synuclein (aSyn) in vulnerable populations of brain cells. Oxidative stress is both a cause and a consequence of aSyn aggregation in the synucleinopathies; however, noninvasive methods for detecting
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The synucleinopathies are a diverse group of neurodegenerative disorders characterized by the accumulation of aggregated alpha-synuclein (aSyn) in vulnerable populations of brain cells. Oxidative stress is both a cause and a consequence of aSyn aggregation in the synucleinopathies; however, noninvasive methods for detecting oxidative stress in living animals have proven elusive. In this study, we used the reactive oxygen species (ROS)-sensitive positron emission tomography (PET) radiotracer [18F]ROStrace to detect increases in oxidative stress in the widely-used A53T mouse model of synucleinopathy. A53T-specific elevations in [18F]ROStrace signal emerged at a relatively early age (6–8 months) and became more widespread within the brain over time, a pattern which paralleled the progressive development of aSyn pathology and oxidative damage in A53T brain tissue. Systemic administration of lipopolysaccharide (LPS) also caused rapid and long-lasting elevations in [18F]ROStrace signal in A53T mice, suggesting that chronic, aSyn-associated oxidative stress may render these animals more vulnerable to further inflammatory insult. Collectively, these results provide novel evidence that oxidative stress is an early and chronic process during the development of synucleinopathy and suggest that PET imaging with [18F]ROStrace holds promise as a means of detecting aSyn-associated oxidative stress noninvasively.
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(This article belongs to the Special Issue Cell Death, Inflammation and Oxidative Stress in Neurodegenerative Diseases: Mechanisms and Cytoprotective Molecules 3.0)
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Open AccessReview
The Mediterranean Diet, Its Microbiome Connections, and Cardiovascular Health: A Narrative Review
by
Vincenzo Abrignani, Andrea Salvo, Gaspare Parrinello and Antonino Tuttolomondo
Int. J. Mol. Sci. 2024, 25(9), 4942; https://doi.org/10.3390/ijms25094942 - 30 Apr 2024
Abstract
The Mediterranean diet (MD), rich in minimally processed plant foods and in monounsaturated fats but low in saturated fats, meat, and dairy products, represents one of the most studied diets for cardiovascular health. It has been shown, from both observational and randomized controlled
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The Mediterranean diet (MD), rich in minimally processed plant foods and in monounsaturated fats but low in saturated fats, meat, and dairy products, represents one of the most studied diets for cardiovascular health. It has been shown, from both observational and randomized controlled trials, that MD reduces body weight, improves cardiovascular disease surrogates such as waist-to-hip ratios, lipids, and inflammation markers, and even prevents the development of fatal and nonfatal cardiovascular disease, diabetes, obesity, and other diseases. However, it is unclear whether it offers cardiovascular benefits from its individual components or as a whole. Furthermore, limitations in the methodology of studies and meta-analyses have raised some concerns over its potential cardiovascular benefits. MD is also associated with characteristic changes in the intestinal microbiota, mediated through its constituents. These include increased growth of species producing short-chain fatty acids, such as Clostridium leptum and Eubacterium rectale, increased growth of Bifidobacteria, Bacteroides, and Faecalibacterium prausnitzii species, and reduced growth of Firmicutes and Blautia species. Such changes are known to be favorably associated with inflammation, oxidative status, and overall metabolic health. This review will focus on the effects of MD on cardiovascular health through its action on gut microbiota.
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(This article belongs to the Section Bioactives and Nutraceuticals)
Open AccessReview
Mechanisms of Pulmonary Vasculopathy in Acute and Long-Term COVID-19: A Review
by
Marianne Riou, Florence Coste, Alain Meyer, Irina Enache, Samy Talha, Anne Charloux, Cyril Reboul and Bernard Geny
Int. J. Mol. Sci. 2024, 25(9), 4941; https://doi.org/10.3390/ijms25094941 - 30 Apr 2024
Abstract
Despite the end of the pandemic, coronavirus disease 2019 (COVID-19) remains a major public health concern. The first waves of the virus led to a better understanding of its pathogenesis, highlighting the fact that there is a specific pulmonary vascular disorder. Indeed, COVID-19
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Despite the end of the pandemic, coronavirus disease 2019 (COVID-19) remains a major public health concern. The first waves of the virus led to a better understanding of its pathogenesis, highlighting the fact that there is a specific pulmonary vascular disorder. Indeed, COVID-19 may predispose patients to thrombotic disease in both venous and arterial circulation, and many cases of severe acute pulmonary embolism have been reported. The demonstrated presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within the endothelial cells suggests that direct viral effects, in addition to indirect effects of perivascular inflammation and coagulopathy, may contribute to pulmonary vasculopathy in COVID-19. In this review, we discuss the pathological mechanisms leading to pulmonary vascular damage during acute infection, which appear to be mainly related to thromboembolic events, an impaired coagulation cascade, micro- and macrovascular thrombosis, endotheliitis and hypoxic pulmonary vasoconstriction. As many patients develop post-COVID symptoms, including dyspnea, we also discuss the hypothesis of pulmonary vascular damage and pulmonary hypertension as a sequela of the infection, which may be involved in the pathophysiology of long COVID.
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(This article belongs to the Special Issue Current Research for Heart Disease Biology and Therapeutics 2.0)
Open AccessCommunication
Availability of Receptors for Advanced Glycation End-Products (RAGE) Influences Differential Transcriptome Expression in Lungs from Mice Exposed to Chronic Secondhand Smoke (SHS)
by
Katrina L. Curtis, Ashley Chang, Ryan Van Slooten, Christian Cooper, Madison N. Kirkham, Thomas Armond, Zack deBernardi, Brett E. Pickett, Juan A. Arroyo and Paul R. Reynolds
Int. J. Mol. Sci. 2024, 25(9), 4940; https://doi.org/10.3390/ijms25094940 - 30 Apr 2024
Abstract
The receptor for advanced glycation end-products (RAGE) has a central function in orchestrating inflammatory responses in multiple disease states including chronic obstructive pulmonary disease (COPD). RAGE is a transmembrane pattern recognition receptor with particular interest in lung disease due to its naturally abundant
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The receptor for advanced glycation end-products (RAGE) has a central function in orchestrating inflammatory responses in multiple disease states including chronic obstructive pulmonary disease (COPD). RAGE is a transmembrane pattern recognition receptor with particular interest in lung disease due to its naturally abundant pulmonary expression. Our previous research demonstrated an inflammatory role for RAGE following acute exposure to secondhand smoke (SHS). However, chronic inflammatory mechanisms associated with RAGE remain ambiguous. In this study, we assessed transcriptional outcomes in mice exposed to chronic SHS in the context of RAGE expression. RAGE knockout (RKO) and wild-type (WT) mice were delivered nose-only SHS via an exposure system for six months and compared to control mice exposed to room air (RA). We specifically compared WT + RA, WT + SHS, RKO + RA, and RKO + SHS. Analysis of gene expression data from WT + RA vs. WT + SHS showed FEZ1, Slpi, and Msln as significant at the three-month time point; while RKO + SHS vs. WT + SHS identified cytochrome p450 1a1 and Slc26a4 as significant at multiple time points; and the RKO + SHS vs. WT + RA revealed Tmem151A as significant at the three-month time point as well as Gprc5a and Dynlt1b as significant at the three- and six-month time points. Notable gene clusters were functionally analyzed and discovered to be specific to cytoskeletal elements, inflammatory signaling, lipogenesis, and ciliogenesis. We found gene ontologies (GO) demonstrated significant biological pathways differentially impacted by the presence of RAGE. We also observed evidence that the PI3K-Akt and NF-κB signaling pathways were significantly enriched in DEGs across multiple comparisons. These data collectively identify several opportunities to further dissect RAGE signaling in the context of SHS exposure and foreshadow possible therapeutic modalities.
Full article
(This article belongs to the Special Issue Advanced Glycation End Products (AGEs) and Their Receptor RAGE)
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