International Journal of Molecular Sciences

23 pages, 6182 KiB

Open AccessArticle

Dependence of Protein Immobilization and Photocurrent Generation in PSI–FTO Electrodes on the Electrodeposition Parameters

by Theresa Kehler, Sebastian Szewczyk and Krzysztof Gibasiewicz

Int. J. Mol. Sci. 2024, 25(18), 9772; https://doi.org/10.3390/ijms25189772 (registering DOI) - 10 Sep 2024

Abstract

This study investigates the immobilization of cyanobacterial photosystem I (PSI) from Synechocystis sp. PCC 6803 onto fluorine-doped tin oxide (FTO) conducting glass plates to create photoelectrodes for biohybrid solar cells. The fabrication of these PSI–FTO photoelectrodes is based on two immobilization processes: rapid [...] Read more.

This study investigates the immobilization of cyanobacterial photosystem I (PSI) from Synechocystis sp. PCC 6803 onto fluorine-doped tin oxide (FTO) conducting glass plates to create photoelectrodes for biohybrid solar cells. The fabrication of these PSI–FTO photoelectrodes is based on two immobilization processes: rapid electrodeposition driven by an external electric field and slower adsorption during solvent evaporation, both influenced by gravitational sedimentation. Deposition and performance of photoelectrodes was investigated by UV–Vis absorption spectroscopy and photocurrent measurements. We investigated the efficiency of PSI immobilization under varying conditions, including solution pH, applied electric field intensity and duration, and electrode polarization, with the goals to control (1) the direction of migration and (2) the orientation of the PSI particles on the substrate surface. Variation in the pH value of the PSI solution alters the surface charge distribution, affecting the net charge and the electric dipole moment of these proteins. Results showed PSI migration to the positively charged electrode at pH 6, 7, and 8, and to the negatively charged electrode at pH 4.4 and 5, suggesting an isoelectric point of PSI between 5 and 6. At acidic pH, the electrophoretic migration was largely hindered by protein aggregation. Notably, photocurrent generation was consistently cathodic and correlated with PSI layer thickness, and no conclusions can be drawn on the orientation of the immobilized proteins. Overall, these findings suggest mediated electron transfer from FTO to PSI by the used electrolyte containing 10 mM sodium ascorbate and 200 μM dichlorophenolindophenol. Full article

(This article belongs to the Special Issue New Insights into Photosystem I)

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14 pages, 2987 KiB

Open AccessArticle

A Visual Distance-Based Capillary Immunoassay Using Biomimetic Polymer Nanoparticles for Highly Sensitive and Specific C-Reactive Protein Quantification

by Ruodong Huang, Zhenbo Liu, Xinlin Jiang, Junqi Huang, Ping Zhou, Zongxia Mou, Dong Ma and Xin Cui

Int. J. Mol. Sci. 2024, 25(18), 9771; https://doi.org/10.3390/ijms25189771 (registering DOI) - 10 Sep 2024

Abstract

The low-cost daily monitoring of C-reactive protein (CRP) levels is crucial for screening acute inflammation or infections as well as managing chronic inflammatory diseases. In this study, we synthesized novel 2-Methacryloyloxy ethyl phosphorylcholine (MPC)-based biomimetic nanoparticles with a large surface area to develop [...] Read more.

The low-cost daily monitoring of C-reactive protein (CRP) levels is crucial for screening acute inflammation or infections as well as managing chronic inflammatory diseases. In this study, we synthesized novel 2-Methacryloyloxy ethyl phosphorylcholine (MPC)-based biomimetic nanoparticles with a large surface area to develop a visual CRP-quantification assay using affordable glass capillaries. The PMPC nanoparticles, synthesized via reflux precipitation polymerization, demonstrated multivalent binding capabilities, enabling rapid and specific CRP capture. In the presence of CRP, PMPC nanoparticles formed sandwich structures with magnetic nanoparticles functionalized with CRP antibodies, thereby enhancing detection sensitivity and specificity. These sandwich complexes were magnetically accumulated into visible and quantifiable stacks within the glass capillaries, allowing for the rapid, sensitive, and specific quantification of CRP concentrations with a detection limit of 57.5 pg/mL and a range spanning from 0 to 5000 ng/mL. The proposed visual distance-based capillary biosensor shows great potential in routine clinical diagnosis as well as point-of-care testing (POCT) in resource-limited settings. Full article

(This article belongs to the Special Issue Recent Research of Nanomaterials in Molecular Science)

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20 pages, 1993 KiB

Open AccessArticle

A New Real-Time Simple Method to Measure the Endogenous Nitrate Reductase Activity (Nar) in Paracoccus denitrificans and Other Denitrifying Bacteria

by José J. García-Trejo, Sharon Rojas-Alcantar, Monserrat Alonso-Vargas, Raquel Ortega, Alejandro Benítez-Guzmán, Leticia Ramírez-Silva, Natalia Pavón, Claudia Peña-Segura, Ofelia Méndez-Romero, Salvador Uribe-Carvajal and Arturo Cadena-Ramírez

Int. J. Mol. Sci. 2024, 25(18), 9770; https://doi.org/10.3390/ijms25189770 (registering DOI) - 10 Sep 2024

Abstract

The transmembrane nitrate reductase (Nar) is the first enzyme in the dissimilatory alternate anaerobic nitrate respiratory chain in denitrifying bacteria. To date, there has been no real-time method to determine its specific activity embedded in its native membrane; here, we describe such a [...] Read more.

The transmembrane nitrate reductase (Nar) is the first enzyme in the dissimilatory alternate anaerobic nitrate respiratory chain in denitrifying bacteria. To date, there has been no real-time method to determine its specific activity embedded in its native membrane; here, we describe such a new method, which is useful with the inside-out membranes of Paracoccus denitrificans and other denitrifying bacteria. This new method takes advantage of the native coupling of the endogenous NADH dehydrogenase or Complex I with the reduction of nitrate by Nar through the quinone pool of the inner membranes of P. denitrificans. This is achieved under previously reached anaerobic conditions. Inner controls confirming the specific Nar activity determined by this new method were made by the total inhibition of the Nar enzyme by sodium azide and cyanide, well-known Nar inhibitors. The estimation of the Michaelis–Menten affinity of Nar for NO₃⁻ using this so-called Nar-JJ assay gave a K_m of 70.4 μM, similar to previously determined values. This new Nar-JJ assay is a suitable, low-cost, and reproducible method to determine in real-time the endogenous Nar activity not only in P. denitrificans, but in other denitrifying bacteria such as Brucella canis, and potentially in other entero-pathogenic bacteria. Full article

(This article belongs to the Special Issue Ion Pumps: Molecular Mechanisms, Structure, Physiology)

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13 pages, 712 KiB

Open AccessArticle

Phylogenetic Lineages and Diseases Associated with Moraxella catarrhalis Isolates Recovered from Bulgarian Patients

by Alexandra S. Alexandrova, Vasil S. Boyanov, Kalina Y. Mihova and Raina T. Gergova

Int. J. Mol. Sci. 2024, 25(18), 9769; https://doi.org/10.3390/ijms25189769 (registering DOI) - 10 Sep 2024

Abstract

Moraxella catarrhalis has been recognized as an important cause of upper respiratory tract and middle ear infections in children, as well as chronic obstructive pulmonary disease and chronic bronchitis in adults. We aim to study the clonal structure, antimicrobial resistance, and serotypes of [...] Read more.

Moraxella catarrhalis has been recognized as an important cause of upper respiratory tract and middle ear infections in children, as well as chronic obstructive pulmonary disease and chronic bronchitis in adults. We aim to study the clonal structure, antimicrobial resistance, and serotypes of M. catarrhalis strains recovered from patients of different ages. Nasopharyngeal swabs, middle ear fluid, and sputum samples were collected. In vitro susceptibility testing was performed according to EUCAST criteria. The monoclonal Ab hybridoma technique was used for serotyping. All strains were subjected to MLST. The studied population demonstrated susceptibility to all tested antimicrobials M. catarrhalis strains, with the majority being serotype A (90.4%), followed by B (6.8%), and C (2.7%). We observed a predominant clonal complex CC224 (21.9%) along with other clusters including CC141 (8.2%), CC184 (8.2%), CC449 (6.8%), CC390 (5.5%), and CC67 (2.7%). Two primary founders, namely, ST224 and ST141, were identified. The analyzed genetic lineages displayed diversity but revealed the predominance of two main clusters, CC224 and CC141, encompassing multidrug-resistant sequence types distributed in other regions. These data underscore the need for ongoing epidemiological monitoring of successfully circulating clones and the implementation of adequate antibiotic policies to limit or delay the spread of multidrug-resistant strains in our region. Full article

(This article belongs to the Section Molecular Microbiology)

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19 pages, 4525 KiB

Open AccessArticle

Mechanistic Insights into Substrate Recognition of Human Nucleoside Diphosphate Kinase C Based on Nucleotide-Induced Structural Changes

by Rezan Amjadi, Sebastiaan Werten, Santosh Kumar Lomada, Clara Baldin, Klaus Scheffzek, Theresia Dunzendorfer-Matt and Thomas Wieland

Int. J. Mol. Sci. 2024, 25(18), 9768; https://doi.org/10.3390/ijms25189768 (registering DOI) - 10 Sep 2024

Abstract

Nucleoside diphosphate kinases (NDPKs) are encoded by nme genes and exist in various isoforms. Based on interactions with other proteins, they are involved in signal transduction, development and pathological processes such as tumorigenesis, metastasis and heart failure. In this study, we report a [...] Read more.

Nucleoside diphosphate kinases (NDPKs) are encoded by nme genes and exist in various isoforms. Based on interactions with other proteins, they are involved in signal transduction, development and pathological processes such as tumorigenesis, metastasis and heart failure. In this study, we report a 1.25 Å resolution structure of human homohexameric NDPK-C bound to ADP and describe the yet unknown complexes formed with GDP, UDP and cAMP, all obtained at a high resolution via X-ray crystallography. Each nucleotide represents a distinct group of mono- or diphosphate purine or pyrimidine bases. We analyzed different NDPK-C nucleotide complexes in the presence and absence of Mg²⁺ and explain how this ion plays an essential role in NDPKs’ phosphotransferase activity. By analyzing a nucleotide-depleted NDPK-C structure, we detected conformational changes upon substrate binding and identify flexible regions in the substrate binding site. A comparison of NDPK-C with other human isoforms revealed a strong similarity in the overall composition with regard to the 3D structure, but significant differences in the charge and hydrophobicity of the isoforms’ surfaces. This may play a role in isoform-specific NDPK interactions with ligands and/or important complex partners like other NDPK isoforms, as well as monomeric and heterotrimeric G proteins. Considering the recently discovered role of NDPK-C in different pathologies, these high-resolution structures thus might provide a basis for interaction studies with other proteins or small ligands, like activators or inhibitors. Full article

(This article belongs to the Special Issue Selected Papers from the 13th International NME Conference: NME/NDPK/AWD 2023)

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20 pages, 4073 KiB

Open AccessArticle

The Vital Role of the CAMTA Gene Family in Phoebe bournei in Response to Drought, Heat, and Light Stress

by Kehui Zheng, Min Li, Zhicheng Yang, Chenyue He, Zekai Wu, Zaikang Tong, Junhong Zhang, Yanzi Zhang and Shijiang Cao

Int. J. Mol. Sci. 2024, 25(18), 9767; https://doi.org/10.3390/ijms25189767 (registering DOI) - 10 Sep 2024

Abstract

The calmodulin-binding transcriptional activator (CAMTA) is a small, conserved gene family in plants that plays a crucial role in regulating growth, development, and responses to various abiotic stress. Given the significance of the CAMTA gene family, various studies have been dedicated to uncovering [...] Read more.

The calmodulin-binding transcriptional activator (CAMTA) is a small, conserved gene family in plants that plays a crucial role in regulating growth, development, and responses to various abiotic stress. Given the significance of the CAMTA gene family, various studies have been dedicated to uncovering its functional characteristics. In this study, genome-wide identification and bioinformatics analysis were conducted to explore CAMTAs in Phoebe bournei. A total of 17 CAMTA genes, each containing at least one domain from CG-1, TIG, ANK, or IQ, were identified in the P. bournei genome. The diversity of PbCAMTAs could be varied depending on their subcellular localization. An analysis of protein motifs, domains, and gene structure revealed that members within the same subgroup exhibited similar organization, supporting the results of the phylogenetic analysis. Gene duplications occurred among members of the PbCAMTA gene family. According to the cis-regulatory element prediction and protein–protein interaction network analysis, eight genes were subjected to qRT-PCR under drought, heat, and light stresses. The expression profiles indicated that PbCAMTAs, particularly PbCAMTA2, PbCAMTA12, and PbCAMTA16, were induced by abiotic stress. This study provides profound insights into the functions of CAMTAs in P. bournei. Full article

(This article belongs to the Section Molecular Plant Sciences)

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13 pages, 2128 KiB

Open AccessArticle

Neutrophil Extracellular Traps Affect Human Inner Ear Vascular Permeability

by Marijana Sekulic, Stavros Giaglis, Nina Chatelain, Daniel Bodmer and Vesna Petkovic

Int. J. Mol. Sci. 2024, 25(18), 9766; https://doi.org/10.3390/ijms25189766 (registering DOI) - 10 Sep 2024

Abstract

The integrity of the blood–labyrinth barrier (BLB) is essential for inner ear homeostasis, regulating the ionic composition of endolymph and perilymph and preventing harmful substance entry. Endothelial hyperpermeability, central in inflammatory and immune responses, is managed through complex intercellular communication and molecular signaling [...] Read more.

The integrity of the blood–labyrinth barrier (BLB) is essential for inner ear homeostasis, regulating the ionic composition of endolymph and perilymph and preventing harmful substance entry. Endothelial hyperpermeability, central in inflammatory and immune responses, is managed through complex intercellular communication and molecular signaling pathways. Recent studies link BLB permeability dysregulation to auditory pathologies like acoustic trauma, autoimmune inner ear diseases, and presbycusis. Polymorphonuclear granulocytes (PMNs), or neutrophils, significantly modulate vascular permeability, impacting endothelial barrier properties. Neutrophil extracellular traps (NETs) are involved in diseases with autoimmune and autoinflammatory bases. The present study evaluated the impact of NETs on a BLB cellular model using a Transwell^® setup. Our findings revealed a concentration-dependent impact of NETs on human inner ear-derived endothelial cells. In particular, endothelial permeability markers increased, as indicated by reduced transepithelial electrical resistance, enhanced dextran permeability, and downregulated junctional gene expression (ZO1, OCL, and CDH5). Changes in cytoskeletal architecture were also observed. These preliminary results pave the way for further research into the potential involvement of NETs in BLB impairment and implications for auditory disorders. Full article

(This article belongs to the Special Issue Hearing Loss: Molecular Biological Insights)

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21 pages, 969 KiB

Open AccessReview

Thyroid Malignancy and Cutaneous Lichen Amyloidosis: Key Points Amid RET Pathogenic Variants in Medullary Thyroid Cancer/Multiple Endocrine Neoplasia Type 2 (MEN2)

by Laura-Semonia Stanescu, Adina Ghemigian, Mihai-Lucian Ciobica, Claudiu Nistor, Adrian Ciuche, Andreea-Maria Radu, Florica Sandru and Mara Carsote

Int. J. Mol. Sci. 2024, 25(18), 9765; https://doi.org/10.3390/ijms25189765 (registering DOI) - 10 Sep 2024

Abstract

We aimed to provide an updated narrative review with respect to the RET pathogenic variants and their implications at the clinical and molecular level in the diagnosis of medullary thyroid cancer (MTC)/multiple endocrine neoplasia (MEN) type 2, particularly with respect to the presence [...] Read more.

We aimed to provide an updated narrative review with respect to the RET pathogenic variants and their implications at the clinical and molecular level in the diagnosis of medullary thyroid cancer (MTC)/multiple endocrine neoplasia (MEN) type 2, particularly with respect to the presence of cutaneous lichen amyloidosis (CLA). We searched English-language, in extenso original articles with no timeline nor study design restriction that were published on PubMed. A traditional interplay stands for CLA and MTC in MEN2 (not MEN3) confirmation. While the connection has been reported for more than three decades, there is still a large gap in understanding and addressing it. The majority of patients with MEN2A-CLA have RET pathogenic variants at codon 634; hence, it suggests an involvement of this specific cysteine residue in both disorders (most data agree that one-third of C634-positive subjects have CLA, but the ranges are between 9% and 50%). Females seem more prone to MEN2-CLA than males. Non-C634 germline RET pathogenic variants included (at a low level of statistical evidence) the following: RET V804M mutation in exon 14 for MTC-CLA (CLA at upper back); RET S891A mutation in exon 15 binding OSMR variant G513D (familial MTC and CLA comprising the lower legs to thighs, upper back, shoulders, arms, and forearms); and C611Y (CLA at interscapular region), respectively. Typically, CLA is detected at an early age (from childhood until young adulthood) before the actual MTC identification unless RET screening protocols are already applied. The time frame between CLA diagnosis and the identification of RET pathogenic variants was between 5 and 60 years according to one study. The same RET mutation in one family is not necessarily associated with the same CLA presentation. In MTC/MEN2 subjects, the most affected CLA area was the scapular region of the upper back. Alternatively, another hypothesis highlighted the fact that CLA is secondary to long-term prurit/notalgia paresthetica (NP) in MTC/MEN2. OSMR p. G513D may play a role in modifying the evolutionary processes of CLA in subjects co-harboring RET mutations (further studies are necessary to sustain this aspect). Awareness in CLA-positive patients is essential, including the decision of RET testing in selected cases. Full article

(This article belongs to the Special Issue New Advances in Thyroid Cancer)

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13 pages, 3134 KiB

Open AccessArticle

Evaluation of a Synthetic Retinoid, Ellorarxine, in the NSC-34 Cell Model of Motor Neuron Disease

by Olivia Escudier, Yunxi Zhang, Andrew Whiting and Paul Chazot

Int. J. Mol. Sci. 2024, 25(18), 9764; https://doi.org/10.3390/ijms25189764 (registering DOI) - 10 Sep 2024

Abstract

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease worldwide and is characterized by progressive muscle atrophy. There are currently two approved treatments, but they only relieve symptoms briefly and do not cure the disease. The main hindrance to research is [...] Read more.

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease worldwide and is characterized by progressive muscle atrophy. There are currently two approved treatments, but they only relieve symptoms briefly and do not cure the disease. The main hindrance to research is the complex cause of ALS, with its pathogenesis not yet fully elucidated. Retinoids (vitamin A derivatives) appear to be essential in neuronal cells and have been implicated in ALS pathogenesis. This study explores 4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydroquinoxalin-2-yl)ethylnyl]benzoic acid (Ellorarxine, or DC645 or NVG0645), a leading synthetic retinoic acid, discussing its pharmacological mechanisms, neuroprotective properties, and relevance to ALS. The potential therapeutic effect of Ellorarxine was analyzed in vitro using the WT and SOD1G93A NSC-34 cell model of ALS at an administered concentration of 0.3–30 nM. Histological, functional, and biochemical analyses were performed. Elorarxine significantly increased MAP2 expression and neurite length, increased AMPA receptor GluA2 expression and raised intracellular Ca²⁺ baseline, increased level of excitability, and reduced Ca²⁺ spike during depolarization in neurites. Ellorarxine also displayed both antioxidant and anti-inflammatory effects. Overall, these results suggest Ellorarxine shows relevance and promise as a novel therapeutic strategy for treatment of ALS. Full article

(This article belongs to the Special Issue Trends in Neuroscience: From Molecular Mechanisms to Innovative Therapeutics)

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16 pages, 6777 KiB

Open AccessArticle

IGF-1 and Glucocorticoid Receptors Are Potential Target Proteins for the NGF-Mimic Effect of β-Cyclocitral from Lavandula angustifolia Mill. in PC12 Cells

by Chenyue An, Lijuan Gao, Lan Xiang and Jianhua Qi

Int. J. Mol. Sci. 2024, 25(18), 9763; https://doi.org/10.3390/ijms25189763 (registering DOI) - 10 Sep 2024

Abstract

In the present study, the PC12 cells as a bioassay system were used to screen the small molecules with nerve growth factor (NGF)- mimic effect from Lavandula angustifolia Mill. The β-Cyclocitral (β-cyc) as an active compound was discovered, and its [...] Read more.

In the present study, the PC12 cells as a bioassay system were used to screen the small molecules with nerve growth factor (NGF)- mimic effect from Lavandula angustifolia Mill. The β-Cyclocitral (β-cyc) as an active compound was discovered, and its chemical structure was also determined. Furthermore, we focused on the bioactive and action mechanism of this compound to do an intensive study with specific protein inhibitors and Western blotting analysis. The β-cyc had novel NGF-mimic and NGF-enhancer effects on PC12 cells, while the insulin-like growth factor-1 receptor (IGF-1R)/phosphatidylinositol 3 kinase, (PI3K)/serine/threonine-protein kinase (AKT), and glucocorticoid receptor (GR)/phospholipase C (PLC)/protein kinase C (PKC) signaling pathways were involved in the bioactivity of β-cyc. In addition, the important role of the rat sarcoma (Ras)/protooncogene serine-threonine protein kinase (Raf) signaling pathway was observed, although it was independent of tyrosine kinase (Trk) receptors. Moreover, the non-label target protein discovery techniques, such as the cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS), were utilized to make predictions of its target protein. The stability of IGF-R and GR, proteins for temperature and protease, was dose-dependently increased after treatment of β-cyc compared with control groups, respectively. These findings indicated that β-cyc promoted the neuron differentiation of PC12 cells via targeting IGF-1R and GR and modification of downstream signaling pathways. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Novel Therapeutic Approaches for Alzheimer’s Disease)

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14 pages, 2853 KiB

Open AccessArticle

OsMBF1a Facilitates Seed Germination by Regulating Biosynthesis of Gibberellic Acid and Abscisic Acid in Rice

by Xin Wang, Ziyun Chen, Jinghua Guo, Xiao Han, Xujian Ji, Meicheng Ke, Feng Yu and Pingfang Yang

Int. J. Mol. Sci. 2024, 25(18), 9762; https://doi.org/10.3390/ijms25189762 (registering DOI) - 10 Sep 2024

Abstract

Seed germination is a pivotal stage in the plant life cycle, orchestrated by a myriad of internal and external factors, notably plant hormones. The underlying molecular mechanisms governing rice seed germination remain largely unelucidated. Herein, we uncover OsMBF1a as a crucial regulatory factor [...] Read more.

Seed germination is a pivotal stage in the plant life cycle, orchestrated by a myriad of internal and external factors, notably plant hormones. The underlying molecular mechanisms governing rice seed germination remain largely unelucidated. Herein, we uncover OsMBF1a as a crucial regulatory factor that employs a dual strategy to promote seed germination: positively activating genes involved in gibberellin (GA) biosynthesis pathways, while negatively regulating key genes responsible for abscisic acid (ABA) synthesis. Furthermore, OsMBF1a modulates the endogenous levels of ABA and GA in rice seeds, reinforcing its central role in the germination process. The expression of ZmMBF1a and ZmMBF1b, the homologous genes in maize, in rice seeds similarly affects germination, indicating the conserved functionality of MBF1 family genes in regulating seed germination. This study provides novel insights into the molecular mechanisms underlying rice seed germination and underscores the significance of MBF1 family genes in plant growth and development. Full article

(This article belongs to the Section Molecular Plant Sciences)

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20 pages, 2634 KiB

Open AccessReview

The Efficacy of Vitamins in the Prevention and Treatment of Cardiovascular Disease

by Paramjit S. Tappia, Anureet K. Shah and Naranjan S. Dhalla

Int. J. Mol. Sci. 2024, 25(18), 9761; https://doi.org/10.3390/ijms25189761 (registering DOI) - 10 Sep 2024

Abstract

Vitamins are known to affect the regulation of several biochemical and metabolic pathways that influence cellular function. Adequate amounts of both hydrophilic and lipophilic vitamins are required for maintaining normal cardiac and vascular function, but their deficiencies can contribute to cardiovascular abnormalities. In [...] Read more.

Vitamins are known to affect the regulation of several biochemical and metabolic pathways that influence cellular function. Adequate amounts of both hydrophilic and lipophilic vitamins are required for maintaining normal cardiac and vascular function, but their deficiencies can contribute to cardiovascular abnormalities. In this regard, a deficiency in the lipophilic vitamins, such as vitamins A, D, and E, as well as in the hydrophilic vitamins, such as vitamin C and B, has been associated with suboptimal cardiovascular function, whereas additional intakes have been suggested to reduce the risk of atherosclerosis, hypertension, ischemic heart disease, arrhythmias, and heart failure. Here, we have attempted to describe the association between low vitamin status and cardiovascular disease, and to offer a discussion on the efficacy of vitamins. While there are inconsistencies in the impact of a deficiency in vitamins on the development of cardiovascular disease and the benefits associated with supplementation, this review proposes that specific vitamins may contribute to the prevention of cardiovascular disease in individuals at risk rather than serve as an adjunct therapy. Full article

(This article belongs to the Special Issue Natural Compounds, Vitamins, and Polyphenols in Cardiovascular and Metabolic Protection)

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13 pages, 9569 KiB

Open AccessArticle

CD26 Is Differentially Expressed throughout the Life Cycle of Infantile Hemangiomas and Characterizes the Proliferative Phase

by Bruno Lorusso, Antonella Nogara, Rodanthi Fioretzaki, Emilia Corradini, Roberta Bove, Giovanni Roti, Andrea Gherli, Anna Montanaro, Gregorio Monica, Filippo Cavazzini, Sabrina Bonomini, Gallia Graiani, Enrico Maria Silini, Letizia Gnetti, Francesco Paolo Pilato, Giuseppe Cerasoli, Federico Quaini and Costanza Anna Maria Lagrasta

Int. J. Mol. Sci. 2024, 25(18), 9760; https://doi.org/10.3390/ijms25189760 (registering DOI) - 10 Sep 2024

Abstract

Infantile hemangiomas (IHs) are benign vascular neoplasms of childhood (prevalence 5–10%) due to the abnormal proliferation of endothelial cells. IHs are characterized by a peculiar natural life cycle enclosing three phases: proliferative (≤12 months), involuting (≥13 months), and involuted (up to 4–7 years). [...] Read more.

Infantile hemangiomas (IHs) are benign vascular neoplasms of childhood (prevalence 5–10%) due to the abnormal proliferation of endothelial cells. IHs are characterized by a peculiar natural life cycle enclosing three phases: proliferative (≤12 months), involuting (≥13 months), and involuted (up to 4–7 years). The mechanisms underlying this neoplastic disease still remain uncovered. Twenty-seven IH tissue specimens (15 proliferative and 12 involuting) were subjected to hematoxylin and eosin staining and a panel of diagnostic markers by immunohistochemistry. WT1, nestin, CD133, and CD26 were also analyzed. Moreover, CD31^pos/CD26^pos proliferative hemangioma–derived endothelial cells (Hem-ECs) were freshly isolated, exposed to vildagliptin (a DPP-IV/CD26 inhibitor), and tested for cell survival and proliferation by MTT assay, FACS analysis, and Western blot assay. All IHs displayed positive CD31, GLUT1, WT1, and nestin immunostaining but were negative for D2-40. Increased endothelial cell proliferation in IH samples was documented by ki67 labeling. All endothelia of proliferative IHs were positive for CD26 (100%), while only 10 expressed CD133 (66.6%). Surprisingly, seven involuting IH samples (58.3%) exhibited coexisting proliferative and involuting aspects in the same hemangiomatous lesion. Importantly, proliferative areas were characterized by CD26 immunolabeling, at variance from involuting sites that were always CD26 negative. Finally, in vitro DPP-IV pharmacological inhibition by vildagliptin significantly reduced Hem-ECs proliferation through the modulation of ki67 and induced cell cycle arrest associated with the upregulation of p21 protein expression. Taken together, our findings suggest that CD26 might represent a reliable biomarker to detect proliferative sites and unveil non-regressive IHs after a 12-month life cycle. Full article

(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)

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12 pages, 918 KiB

Open AccessReview

Neuroinflammation and Brain Health Risks in Veterans Exposed to Burn Pit Toxins

by Athena W. Brooks, Brian J. Sandri, Joshua P. Nixon, Timothy R. Nurkiewicz, Paul Barach, Janeen H. Trembley and Tammy A. Butterick

Int. J. Mol. Sci. 2024, 25(18), 9759; https://doi.org/10.3390/ijms25189759 (registering DOI) - 10 Sep 2024

Abstract

Military burn pits, used for waste disposal in combat zones, involve the open-air burning of waste materials, including plastics, metals, chemicals, and medical waste. The pits release a complex mixture of occupational toxic substances, including particulate matter (PM), volatile organic compounds (VOCs), heavy [...] Read more.

Military burn pits, used for waste disposal in combat zones, involve the open-air burning of waste materials, including plastics, metals, chemicals, and medical waste. The pits release a complex mixture of occupational toxic substances, including particulate matter (PM), volatile organic compounds (VOCs), heavy metals, dioxins, and polycyclic aromatic hydrocarbons (PAHs). Air pollution significantly impacts brain health through mechanisms involving neuroinflammation. Pollutants penetrate the respiratory system, enter the bloodstream, and cross the blood–brain barrier (BBB), triggering inflammatory responses in the central nervous system (CNS). Chronic environmental exposures result in sustained inflammation, oxidative stress, and neuronal damage, contributing to neurodegenerative diseases and cognitive impairment. Veterans exposed to burn pit toxins are particularly at risk, reporting higher rates of respiratory issues, neurological conditions, cognitive impairments, and mental health disorders. Studies demonstrate that Veterans exposed to these toxins have higher rates of neuroinflammatory markers, accelerated cognitive decline, and increased risks of neurodegenerative diseases. This narrative review synthesizes the research linking airborne pollutants such as PM, VOCs, and heavy metals to neuroinflammatory processes and cognitive effects. There is a need for targeted interventions to mitigate the harmful and escalating effects of environmental air pollution exposures on the CNS, improving public health outcomes for vulnerable populations, especially for Veterans exposed to military burn pit toxins. Full article

(This article belongs to the Special Issue Immunity in Neurodegenerative Diseases: Systemic Immune Imbalance, Neuroinflammation, and Beyond)

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13 pages, 1057 KiB

Open AccessReview

The Protective Role of Interleukin-37 in Cardiovascular Diseases through Ferroptosis Modulation

by Alfredo Cruz-Gregorio, Luis M. Amezcua-Guerra, Brandon Fisher-Bautista, Abraham Romero-Beltrán and Gabriela Fonseca-Camarillo

Int. J. Mol. Sci. 2024, 25(18), 9758; https://doi.org/10.3390/ijms25189758 (registering DOI) - 10 Sep 2024

Abstract

The role of ferroptosis and iron metabolism dysregulation in the pathophysiology of cardiovascular diseases is increasingly recognized. Conditions such as hypertension, cardiomyopathy, atherosclerosis, myocardial ischemia/reperfusion injury, heart failure, and cardiovascular complications associated with COVID-19 have been linked to these processes. Inflammation is central [...] Read more.

The role of ferroptosis and iron metabolism dysregulation in the pathophysiology of cardiovascular diseases is increasingly recognized. Conditions such as hypertension, cardiomyopathy, atherosclerosis, myocardial ischemia/reperfusion injury, heart failure, and cardiovascular complications associated with COVID-19 have been linked to these processes. Inflammation is central to these conditions, prompting exploration into the inflammatory and immunoregulatory molecular pathways that mediate ferroptosis and its contribution to cardiovascular disease progression. Notably, emerging evidence highlights interleukin-37 as a protective cytokine with the ability to activate the nuclear factor erythroid 2-related factor 2 pathway, inhibit macrophage ferroptosis, and attenuate atherosclerosis progression in murine models. However, a comprehensive review focusing on interleukin-37 and its protective role against ferroptosis in CVD is currently lacking. This review aims to fill this gap by summarizing existing knowledge on interleukin-37, including its regulatory functions and impact on ferroptosis in conditions such as atherosclerosis and myocardial infarction. We also explore experimental strategies and propose that targeting interleukin-37 to modulate ferroptosis presents a promising therapeutic approach for the prevention and treatment of cardiovascular diseases. Full article

(This article belongs to the Special Issue Novel Biomarkers for Cardiovascular Diseases)

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Int. J. Mol. Sci., Volume 25, Issue 18 (September-2 2024) – 15 articles

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