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 and 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:
4.9 (2023);
5-Year Impact Factor:
5.6 (2023)
Latest Articles
Disulfidptosis: A Novel Prognostic Criterion and Potential Treatment Strategy for Diffuse Large B-Cell Lymphoma (DLBCL)
Int. J. Mol. Sci. 2024, 25(13), 7156; https://doi.org/10.3390/ijms25137156 (registering DOI) - 28 Jun 2024
Abstract
Diffuse Large B-cell Lymphoma (DLBCL), with its intrinsic genetic and epigenetic heterogeneity, exhibits significantly variable clinical outcomes among patients treated with the current standard regimen. Disulfidptosis, a novel form of regulatory cell death triggered by disulfide stress, is characterized by the collapse of
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Diffuse Large B-cell Lymphoma (DLBCL), with its intrinsic genetic and epigenetic heterogeneity, exhibits significantly variable clinical outcomes among patients treated with the current standard regimen. Disulfidptosis, a novel form of regulatory cell death triggered by disulfide stress, is characterized by the collapse of cytoskeleton proteins and F-actin due to intracellular accumulation of disulfides. We investigated the expression variations of disulfidptosis-related genes (DRGs) in DLBCL using two publicly available gene expression datasets. The initial analysis of DRGs in DLBCL (GSE12453) revealed differences in gene expression patterns between various normal B cells and DLBCL. Subsequent analysis (GSE31312) identified DRGs strongly associated with prognostic outcomes, revealing eight characteristic DRGs (CAPZB, DSTN, GYS1, IQGAP1, MYH9, NDUFA11, NDUFS1, OXSM). Based on these DRGs, DLBCL patients were stratified into three groups, indicating that (1) DRGs can predict prognosis, and (2) DRGs can help identify novel therapeutic candidates. This study underscores the significant role of DRGs in various biological processes within DLBCL. Assessing the risk scores of individual DRGs allows for more precise stratification of prognosis and treatment strategies for DLBCL patients, thereby enhancing the effectiveness of clinical practice.
Full article
(This article belongs to the Section Molecular Oncology)
Open AccessArticle
Regulatory Effects of 198-bp Structural Variants in the GSTA2 Promoter Region on Adipogenesis in Chickens
by
Wangyu Li, Meng Xu, Zihao Zhang, Jiaying Liang, Rong Fu, Wujian Lin, Wen Luo, Xiquan Zhang and Tuanhui Ren
Int. J. Mol. Sci. 2024, 25(13), 7155; https://doi.org/10.3390/ijms25137155 (registering DOI) - 28 Jun 2024
Abstract
Molecular breeding accelerates animal breeding and improves efficiency by utilizing genetic mutations. Structural variations (SVs), a significant source of genetic mutations, have a greater impact on phenotypic variation than SNPs. Understanding SV functional mechanisms and obtaining precise information are crucial for molecular breeding.
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Molecular breeding accelerates animal breeding and improves efficiency by utilizing genetic mutations. Structural variations (SVs), a significant source of genetic mutations, have a greater impact on phenotypic variation than SNPs. Understanding SV functional mechanisms and obtaining precise information are crucial for molecular breeding. In this study, association analysis revealed significant correlations between 198-bp SVs in the GSTA2 promoter region and abdominal fat weight, intramuscular fat content, and subcutaneous fat thickness in chickens. High expression of GSTA2 in adipose tissue was positively correlated with the abdominal fat percentage, and different genotypes of GSTA2 exhibited varied expression patterns in the liver. The 198-bp SVs regulate GSTA2 expression by binding to different transcription factors. Overexpression of GSTA2 promoted preadipocyte proliferation and differentiation, while interference had the opposite effect. Mechanistically, the 198-bp fragment contains binding sites for transcription factors such as C/EBPα that regulate GSTA2 expression and fat synthesis. These SVs are significantly associated with chicken fat traits, positively influencing preadipocyte development by regulating cell proliferation and differentiation. Our work provides compelling evidence for the use of 198-bp SVs in the GSTA2 promoter region as molecular markers for poultry breeding and offers new insights into the pivotal role of the GSTA2 gene in fat generation.
Full article
(This article belongs to the Section Molecular Genetics and Genomics)
Open AccessArticle
The Effects of Different Doses of Canthaxanthin in the Diet of Laying Hens on Egg Quality, Physical Characteristics, Metabolic Mechanism, and Offspring Health
by
Junnan Zhang, Zhiqiong Mao, Jiangxia Zheng, Congjiao Sun and Guiyun Xu
Int. J. Mol. Sci. 2024, 25(13), 7154; https://doi.org/10.3390/ijms25137154 (registering DOI) - 28 Jun 2024
Abstract
Currently, there is a dearth of in-depth analysis and research on the impact of canthaxanthin on the production performance, egg quality, physical characteristics, and offspring health of laying hens. Furthermore, the metabolic mechanism of cantharidin in the body remains unclear. Therefore, to solve
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Currently, there is a dearth of in-depth analysis and research on the impact of canthaxanthin on the production performance, egg quality, physical characteristics, and offspring health of laying hens. Furthermore, the metabolic mechanism of cantharidin in the body remains unclear. Therefore, to solve the above issues in detail, our study was conducted with a control group (C group), a low-dose canthaxanthin group (L group), and a high-dose canthaxanthin group (H group), each fed for a period of 40 days. Production performance was monitored during the experiment, in which L and H groups showed a significant increase in ADFI. Eggs were collected for quality analysis, revealing no significant differences in qualities except for yolk color (YC). The YC of the C group almost did not change, ranging from 6.08 to 6.20; however, the trend in YC change in other groups showed an initial intense increase, followed by a decrease, and eventually reached dynamic equilibrium. By detecting the content of canthaxanthin in the yolk, the YC change trend was found to be correlated with canthaxanthin levels in the yolk. The content of unsaturated fatty acid increased slightly in L and H groups. Following the incubation period, the physical characteristics and blood biochemical indices of chicks were evaluated. It was observed that the shank color of chicks in the L and H groups was significantly higher than that in the C group at birth. However, by the 35th day, there were no significant differences in shank color among the three groups. Further investigation into the metabolic mechanism involving canthaxanthin revealed that the substance underwent incomplete metabolism upon entering the body, resulting in its accumulation as well as metabolic by-product accumulation in the yolk. In summary, this study highlighted the importance of understanding canthaxanthin’s role in production performance, egg quality, and offspring health, providing valuable insights for breeders to optimize feeding strategies.
Full article
(This article belongs to the Special Issue Advances in Animal Models in Biomedical Research, 2nd Edition)
Open AccessEditorial
Special Issue “Antimicrobial Biomaterials: Recent Progress”
by
Helena P. Felgueiras
Int. J. Mol. Sci. 2024, 25(13), 7153; https://doi.org/10.3390/ijms25137153 (registering DOI) - 28 Jun 2024
Abstract
Biomaterials have demonstrated their ability to serve as effective drug delivery platforms, enabling targeted and localized administration of therapeutic agents. [...]
Full article
(This article belongs to the Special Issue Antimicrobial Biomaterials: Recent Progress)
Open AccessArticle
Bioreduction of 4′-Hydroxychalcone in Deep Eutectic Solvents: Optimization and Efficacy with Various Yeast Strains
by
Paweł Chlipała, Tomasz Janeczko and Marcelina Mazur
Int. J. Mol. Sci. 2024, 25(13), 7152; https://doi.org/10.3390/ijms25137152 (registering DOI) - 28 Jun 2024
Abstract
4′-dihydrochalcones are secondary metabolites isolated from many medicinal plants and from the resin known as ‘dragon’s blood’. Due to their biological potential, our research objective was to determine the possibilities of using biocatalysis processes carried out in deep eutectic solvents (DESs) to obtain
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4′-dihydrochalcones are secondary metabolites isolated from many medicinal plants and from the resin known as ‘dragon’s blood’. Due to their biological potential, our research objective was to determine the possibilities of using biocatalysis processes carried out in deep eutectic solvents (DESs) to obtain 4′-dihydrochalcones as a model compound. The processes were carried out in a culture of the yeast Yarrowia lipolytica KCh 71 and also in cultures of strains of the genera Rhodotorula and Debaryomyces. Based on the experiments carried out, an optimum process temperature of 35 °C was chosen, and the most suitable DES contained glycerol as a hydrogen bond donor (HBD). For a medium with 30% water content (DES 11), the conversion observed after 24 h exceeded 70%, while increasing the amount of water to 50% resulted in a similar level of conversion after just 1 h. A fivefold increase in the amount of added substrate resulted in a reduction in conversion, which reached 30.3%. Of the other yeast strains tested, Rhodotorula marina KCh 77 and Rhodotorula rubra KCh 4 also proved to be good biocatalysts for the bioreduction process. For these strains, the conversion reached 95.4% and 95.1%, respectively. These findings highlight the potential of yeast as a biocatalyst for the selective reduction of α,β-unsaturated ketones and the possibility of using a DESs as a reaction medium in this process.
Full article
(This article belongs to the Special Issue Rational Design and Synthesis of Bioactive Molecules)
Open AccessReview
New Origins of Yeast, Plant and Bacterial-Derived Extracellular Vesicles to Expand and Advance Compound Delivery
by
María Fernández-Rhodes, Cristina Lorca, Julia Lisa, Iolanda Batalla, Alfredo Ramos-Miguel, Xavier Gallart-Palau and Aida Serra
Int. J. Mol. Sci. 2024, 25(13), 7151; https://doi.org/10.3390/ijms25137151 (registering DOI) - 28 Jun 2024
Abstract
Extracellular vesicles (EVs) constitute a sophisticated molecular exchange mechanism highly regarded for their potential as a next-generation platform for compound delivery. However, identifying sustainable and biologically safe sources of EVs remains a challenge. This work explores the emergence of novel sources of plant
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Extracellular vesicles (EVs) constitute a sophisticated molecular exchange mechanism highly regarded for their potential as a next-generation platform for compound delivery. However, identifying sustainable and biologically safe sources of EVs remains a challenge. This work explores the emergence of novel sources of plant and bacterial-based EVs, such as those obtained from food industry by-products, known as BP-EVs, and their potential to be used as safer and biocompatible nanocarriers, addressing some of the current challenges of the field. These novel sources exhibit remarkable oral bioavailability and biodistribution, with minimal cytotoxicity and a selective targeting capacity toward the central nervous system, liver, and skeletal tissues. Additionally, we review the ease of editing these recently uncovered nanocarrier-oriented vesicles using common EV editing methods, examining the cargo-loading processes applicable to these sources, which involve both passive and active functionalization methods. While the primary focus of these novel sources of endogenous EVs is on molecule delivery to the central nervous system and skeletal tissue based on their systemic target preference, their use, as reviewed here, extends beyond these key applications within the biotechnological and biomedical fields.
Full article
(This article belongs to the Special Issue Biological Functions and Therapeutic Applications of Extracellular Vesicles)
Open AccessArticle
Dietary Supplementation with n-3 Polyunsaturated Fatty Acids Delays the Phenotypic Manifestation of Krabbe Disease and Partially Restores Lipid Mediator Production in the Brain—Study in a Mouse Model of the Disease
by
Cinzia Signorini, Giovanna Pannuzzo, Adriana Carol Eleonora Graziano, Elena Moretti, Giulia Collodel and Venera Cardile
Int. J. Mol. Sci. 2024, 25(13), 7149; https://doi.org/10.3390/ijms25137149 (registering DOI) - 28 Jun 2024
Abstract
Lipid mediators from fatty acid oxidation have been shown to be associated with the severity of Krabbe disease (KD), a disorder linked to mutations in the galactosylceramidase (GALC) gene. This study aims to investigate the effects of n-3 polyunsaturated fatty
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Lipid mediators from fatty acid oxidation have been shown to be associated with the severity of Krabbe disease (KD), a disorder linked to mutations in the galactosylceramidase (GALC) gene. This study aims to investigate the effects of n-3 polyunsaturated fatty acid (PUFA) supplementation on KD traits and fatty acid metabolism using Twitcher (Tw) animals as a natural model for KD. Wild-type (Wt), heterozygous (Ht), and affected Tw animals were treated orally with 36 mg n-3 PUFAs/kg body weight/day from 10 to 35 days of life. The end product of PUFA peroxidation (8-isoprostane), the lipid mediator involved in the resolution of inflammatory exudates (resolvin D1), and the total amount of n-3 PUFAs were analyzed in the brains of mice. In Tw mice, supplementation with n-3 PUFAs delayed the manifestation of disease symptoms (p < 0.0001), and in the bran, decreased 8-isoprostane amounts (p < 0.0001), increased resolvin D1 levels (p < 0.005) and increased quantity of total n-3 PUFAs (p < 0.05). Furthermore, total brain n-3 PUFA levels were associated with disease severity (r = −0.562, p = 0.0001), resolvin D1 (r = 0.712, p < 0.0001), and 8-isoprostane brain levels (r = −0.690, p < 0.0001). For the first time in a natural model of KD, brain levels of n-3 PUFAs are shown to determine disease severity and to be involved in the peroxidation of brain PUFAs as well as in the production of pro-resolving lipid mediators. It is also shown that dietary supplementation with n-3 PUFAs leads to a slowing of the phenotypic presentation of the disease and restoration of lipid mediator production.
Full article
(This article belongs to the Special Issue Fatty Acid Oxidation in Diseases)
Open AccessArticle
Pilot Study for Isolation of Stromal Vascular Fraction with Collagenase Using an Automated Processing System
by
Gershon Zinger, Yoav Gronovich, Adi Maisel Lotan and Racheli Sharon-Gabbay
Int. J. Mol. Sci. 2024, 25(13), 7148; https://doi.org/10.3390/ijms25137148 (registering DOI) - 28 Jun 2024
Abstract
There are many potential therapeutic applications for autologous adipose-derived stromal cells. These cells are found in a heterogeneous population isolated from adipose tissue called the stromal vascular fraction (SVF). Closed automated systems are available to release cells from the adherent stroma. Here, we
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There are many potential therapeutic applications for autologous adipose-derived stromal cells. These cells are found in a heterogeneous population isolated from adipose tissue called the stromal vascular fraction (SVF). Closed automated systems are available to release cells from the adherent stroma. Here, we test one system to evaluate the heterogeneous output for yield, purity, cellular characterization, and stemness criteria. The SVF was isolated from three donors using the Automated Cell Station (ACS) from BSL Co., Ltd., Busan, Republic of Korea. The SVF cellular output was characterized for cell yield and viability, immunophenotyping analysis, pluripotent differentiation potential, adhesion to plastic, and colony-forming units. Additionally, the SVF was tested for endotoxin and collagenase residuals. The SVF yield from the ACS system was an average volume of 7.9 ± 0.5 mL containing an average of 19 × 106 nucleated cells with 85 ± 12% viability. Flow cytometry identified a variety of cells, including ASCs (23%), macrophages (24%), endothelial cells (5%), pericytes (4%), and transitional cells (0.5%). The final concentrated product contained cells capable of differentiating into adipogenic, chondrogenic, and osteogenic phenotypes. Furthermore, tests for SVF sterility and purity showed no evidence of endotoxin or collagenase residuals. The ACS system can efficiently process cells from adipose tissue within the timeframe of a single surgical procedure. The cellular characterization indicated that this system can yield a sterile and concentrated SVF output, providing a valuable source of ASCs within the heterogeneous cell population.
Full article
(This article belongs to the Topic Pluripotent Stem Cells)
Open AccessReview
Beef Cattle Genome Project: Advances in Genome Sequencing, Assembly, and Functional Genes Discovery
by
Zhendong Gao, Ying Lu, Yuqing Chong, Mengfei Li, Jieyun Hong, Jiao Wu, Dongwang Wu, Dongmei Xi and Weidong Deng
Int. J. Mol. Sci. 2024, 25(13), 7147; https://doi.org/10.3390/ijms25137147 (registering DOI) - 28 Jun 2024
Abstract
Beef is a major global source of protein, playing an essential role in the human diet. The worldwide production and consumption of beef continue to rise, reflecting a significant trend. However, despite the critical importance of beef cattle resources in agriculture, the diversity
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Beef is a major global source of protein, playing an essential role in the human diet. The worldwide production and consumption of beef continue to rise, reflecting a significant trend. However, despite the critical importance of beef cattle resources in agriculture, the diversity of cattle breeds faces severe challenges, with many breeds at risk of extinction. The initiation of the Beef Cattle Genome Project is crucial. By constructing a high-precision functional annotation map of their genome, it becomes possible to analyze the genetic mechanisms underlying important traits in beef cattle, laying a solid foundation for breeding more efficient and productive cattle breeds. This review details advances in genome sequencing and assembly technologies, iterative upgrades of the beef cattle reference genome, and its application in pan-genome research. Additionally, it summarizes relevant studies on the discovery of functional genes associated with key traits in beef cattle, such as growth, meat quality, reproduction, polled traits, disease resistance, and environmental adaptability. Finally, the review explores the potential of telomere-to-telomere (T2T) genome assembly, structural variations (SVs), and multi-omics techniques in future beef cattle genetic breeding. These advancements collectively offer promising avenues for enhancing beef cattle breeding and improving genetic traits.
Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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Open AccessArticle
OsPUB9 Gene Edited by CRISPR/Cas9 Enhanced Resistance to Bacterial Leaf Blight in Rice (Oryza sativa L.)
by
Me-Sun Kim, Van Trang Le, Yu Jin Jung, Kwon-Kyoo Kang and Yong-Gu Cho
Int. J. Mol. Sci. 2024, 25(13), 7145; https://doi.org/10.3390/ijms25137145 (registering DOI) - 28 Jun 2024
Abstract
Ubiquitination plays a crucial role in regulating signal pathways during the post-translation stage of protein synthesis in response to various environmental stresses. E3 ubiquitin ligase has been discovered to ultimately control various intracellular activities by imparting specificity to proteins to be degraded. This
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Ubiquitination plays a crucial role in regulating signal pathways during the post-translation stage of protein synthesis in response to various environmental stresses. E3 ubiquitin ligase has been discovered to ultimately control various intracellular activities by imparting specificity to proteins to be degraded. This study was conducted to confirm biological and genetic functions of the U-box type E3 ubiquitin ligase (PUB) gene against biotic stress in rice (Oryza sativa L.). OsPUB9 gene-specific sgRNA were designed and transformants were developed through Agrobacterium-mediated transformation. Deep sequencing using callus was performed to confirm the mutation type of T0 plants, and a total of three steps were performed to select null individuals without T-DNA insertion. In the case of the OsPUB9 gene-edited line, a one bp insertion was generated by gene editing, and it was confirmed that early stop codon and multiple open reading frame (ORF) sites were created by inserting thymine. It is presumed that ubiquitination function also changed according to the change in protein structure of U-box E3 ubiquitin ligase. The OsPUB9 gene-edited null lines were inoculated with bacterial leaf blight, and finally confirmed to have a resistance phenotype similar to Jinbaek, a bacterial blight-resistant cultivar. Therefore, it is assumed that the amino acid sequence derived from the OsPUB9 gene is greatly changed, resulting in a loss of the original protein functions related to biological mechanisms. Comprehensively, it was confirmed that resistance to bacterial leaf blight stress was enhanced when a mutation occurred at a specific site of the OsPUB9 gene.
Full article
(This article belongs to the Special Issue Responses to Abiotic and Biotic Stresses of Gene-Edited Crop Plants)
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Open AccessReview
Role of Kynurenine and Its Derivatives in the Neuroimmune System
by
Makoto Fujikawa, Masashi Ueda and Kenta Maruyama
Int. J. Mol. Sci. 2024, 25(13), 7144; https://doi.org/10.3390/ijms25137144 (registering DOI) - 28 Jun 2024
Abstract
In recent years, there has been a growing realization of intricate interactions between the nervous and immune systems, characterized by shared humoral factors and receptors. This interplay forms the basis of the neuroimmune system, the understanding of which will provide insights into the
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In recent years, there has been a growing realization of intricate interactions between the nervous and immune systems, characterized by shared humoral factors and receptors. This interplay forms the basis of the neuroimmune system, the understanding of which will provide insights into the pathogenesis of neurological diseases, in which the involvement of the immune system has been overlooked. Kynurenine and its derivatives derived from tryptophan have long been implicated in the pathogenesis of various neurological diseases. Recent studies have revealed their close association not only with neurological disorders but also with sepsis-related deaths. This review provides an overview of the biochemistry of kynurenine and its derivatives, followed by a discussion of their role via the modulation of the neuroimmune system in various diseases.
Full article
(This article belongs to the Special Issue Kynurenic Acid: Emerging Research Advances and Therapeutic Implications)
Open AccessReview
Progress in the Study of Fra-2 in Respiratory Diseases
by
Shuping Zheng and Yun Liu
Int. J. Mol. Sci. 2024, 25(13), 7143; https://doi.org/10.3390/ijms25137143 (registering DOI) - 28 Jun 2024
Abstract
Fos-related antigen-2 (Fra-2) is a member of the activator protein 1 (AP-1) family of transcription factors. It is involved in controlling cell growth and differentiation by regulating the production of the extracellular matrix and coordinating the balance of signals within and outside the
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Fos-related antigen-2 (Fra-2) is a member of the activator protein 1 (AP-1) family of transcription factors. It is involved in controlling cell growth and differentiation by regulating the production of the extracellular matrix and coordinating the balance of signals within and outside the cell. Fra-2 is not only closely related to bone development, metabolism, and immune system and eye development but also in the progression of respiratory conditions like lung tumors, asthma, pulmonary fibrosis, and chronic obstructive pulmonary disease (COPD). The increased expression and activation of Fra-2 in various lung diseases has been shown in several studies. However, the specific molecular mechanisms through which Fra-2 affects the development of respiratory diseases are not yet understood. The purpose of this research is to summarize and delineate advancements in the study of the involvement of transcription factor Fra-2 in disorders related to the respiratory system.
Full article
(This article belongs to the Special Issue Molecular Dynamics Simulations and Structural Analysis of Protein Domains)
Open AccessReview
Genetic and Molecular Biomarkers in Aggressive Pheochromocytomas and Paragangliomas
by
Francesca Torresan, Clelia Iacobone, Francesco Giorgino and Maurizio Iacobone
Int. J. Mol. Sci. 2024, 25(13), 7142; https://doi.org/10.3390/ijms25137142 (registering DOI) - 28 Jun 2024
Abstract
Pheochromocytomas and paragangliomas (PPGLs) are rare neoplasms producing catecholamines that occur as hereditary syndromes in 25–40% of cases. To date, PPGLs are no longer classified as benign and malignant tumors since any lesion could theoretically metastasize, even if it occurs only in a
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Pheochromocytomas and paragangliomas (PPGLs) are rare neoplasms producing catecholamines that occur as hereditary syndromes in 25–40% of cases. To date, PPGLs are no longer classified as benign and malignant tumors since any lesion could theoretically metastasize, even if it occurs only in a minority of cases (approximately 10–30%). Over the last decades, several attempts were made to develop a scoring system able to predict the risk of aggressive behavior at diagnosis, including the risk of metastases and disease recurrence; unfortunately, none of the available scores is able to accurately predict the risk of aggressive behavior, even including clinical, biochemical, and histopathological features. Thus, life-long follow-up is required in PPGL patients. Some recent studies focusing on genetic and molecular markers (involved in hypoxia regulation, gene transcription, cellular growth, differentiation, signaling pathways, and apoptosis) seem to indicate they are promising prognostic factors, even though their clinical significance needs to be further evaluated. The most involved pathways in PPGLs with aggressive behavior are represented by Krebs cycle alterations caused by succinate dehydrogenase subunits (SDHx), especially when caused by SDHB mutations, and by fumarate hydratase mutations that lead to the activation of hypoxia pathways and DNA hypermethylation, suggesting a common pathway in tumorigenesis. Conversely, PPGLs showing mutations in the kinase cascade (cluster 2) tend to display less aggressive behavior. Finally, establishing pathways of tumorigenesis is also fundamental to developing new drugs targeted to specific pathways and improving the survival of patients with metastatic disease. Unfortunately, the rarity of these tumors and the scarce number of cases enrolled in the available studies represents an obstacle to validating the role of molecular markers as reliable predictors of aggressiveness.
Full article
(This article belongs to the Special Issue Molecular Aspects of Adrenal Diseases and Carcinoma)
Open AccessArticle
Chronic HIV Infection Increases Monocyte NLRP3 Inflammasome-Dependent IL-1α and IL-1β Release
by
Hedda Hoel, Tuva Børresdatter Dahl, Kuan Yang, Linda Gail Skeie, Annika Elisabet Michelsen, Thor Ueland, Jan Kristian Damås, Anne Ma Dyrhol-Riise, Børre Fevang, Arne Yndestad, Pål Aukrust, Marius Trøseid and Øystein Sandanger
Int. J. Mol. Sci. 2024, 25(13), 7141; https://doi.org/10.3390/ijms25137141 (registering DOI) - 28 Jun 2024
Abstract
Antiretroviral treatment (ART) has converted HIV from a lethal disease to a chronic condition, yet co-morbidities persist. Incomplete immune recovery and chronic immune activation, especially in the gut mucosa, contribute to these complications. Inflammasomes, multi-protein complexes activated by innate immune receptors, appear to
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Antiretroviral treatment (ART) has converted HIV from a lethal disease to a chronic condition, yet co-morbidities persist. Incomplete immune recovery and chronic immune activation, especially in the gut mucosa, contribute to these complications. Inflammasomes, multi-protein complexes activated by innate immune receptors, appear to play a role in these inflammatory responses. In particular, preliminary data indicate the involvement of IFI16 and NLRP3 inflammasomes in chronic HIV infection. This study explores inflammasome function in monocytes from people with HIV (PWH); 22 ART-treated with suppressed viremia and 17 untreated PWH were compared to 33 HIV-negative donors. Monocytes were primed with LPS and inflammasomes activated with ATP in vitro. IFI16 and NLRP3 mRNA expression were examined in a subset of donors. IFI16 and NLRP3 expression in unstimulated monocytes correlated negatively with CD4 T cell counts in untreated PWH. For IFI16, there was also a positive correlation with viral load. Monocytes from untreated PWH exhibit increased release of IL-1α, IL-1β, and TNF compared to treated PWH and HIV-negative donors. However, circulating monocytes in PWH are not pre-primed for inflammasome activation in vivo. The findings suggest a link between IFI16, NLRP3, and HIV progression, emphasizing their potential role in comorbidities such as cardiovascular disease. The study provides insights into inflammasome regulation in HIV pathogenesis and its implications for therapeutic interventions.
Full article
(This article belongs to the Special Issue Role of NLRP3 Inflammasome in Inflammatory and Immunological Diseases)
Open AccessArticle
BK Channels in Tail Artery Vascular Smooth Muscle Cells of Normotensive (WKY) and Hypertensive (SHR) Rats Possess Similar Calcium Sensitivity but Different Responses to the Vasodilator Iloprost
by
Anastasia Pyanova, Vladimir N. Serebryakov, Hristo Gagov, Mitko Mladenov and Rudolf Schubert
Int. J. Mol. Sci. 2024, 25(13), 7140; https://doi.org/10.3390/ijms25137140 (registering DOI) - 28 Jun 2024
Abstract
It has been reported that, in the spontaneously hypertensive rat (SHR) model of hypertension, different components of the G-protein/adenylate cyclase (AC)/Calcium-activated potassium channel of high conductance (BK) channel signaling pathway are altered differently. In the upstream part of the pathway (G-protein/AC), a comparatively
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It has been reported that, in the spontaneously hypertensive rat (SHR) model of hypertension, different components of the G-protein/adenylate cyclase (AC)/Calcium-activated potassium channel of high conductance (BK) channel signaling pathway are altered differently. In the upstream part of the pathway (G-protein/AC), a comparatively low efficacy has been established, whereas downstream BK currents seem to be increased. Thus, the overall performance of this signaling pathway in SHR is elusive. For a better understanding, we focused on one aspect, the direct targeting of the BK channel by the G-protein/AC pathway and tested the hypothesis that the comparatively low AC pathway efficacy in SHR results in a reduced agonist-induced stimulation of BK currents. This hypothesis was investigated using freshly isolated smooth muscle cells from WKY and SHR rat tail artery and the patch-clamp technique. It was observed that: (1) single BK channels have similar current–voltage relationships, voltage-dependence and calcium sensitivity; (2) BK currents in cells with a strong buffering of the BK channel activator calcium have similar current–voltage relationships; (3) the iloprost-induced concentration-dependent increase of the BK current is larger in WKY compared to SHR; (4) the effects of activators of the PKA pathway, the catalytic subunit of PKA and the potent and selective cAMP-analogue Sp-5,6-DCl-cBIMPS on BK currents are similar. Thus, our data suggest that the lower iloprost-induced stimulation of the BK current in freshly isolated rat tail artery smooth muscle cells from SHR compared with WKY is due to the lower efficacy of upstream elements of the G-Protein/AC/BK channel pathway.
Full article
(This article belongs to the Special Issue Role of Ion Channels in Cardiovascular and Other Human Diseases)
Open AccessArticle
Long-Chain Alkylthio Cyclodextrin Derivatives for Modulation of Quorum-Sensing-Based Bioluminescence in Aliivibrio fischeri Model System
by
Éva Fenyvesi, Zsófia Berkl, Laura Ligethy, Ildikó Fekete-Kertész, Márton Csizmazia, Milo Malanga, István Puskás, Levente Szőcs, Róbert Iványi, István Kese, Erzsébet Varga, Lajos Szente and Mónika Molnár
Int. J. Mol. Sci. 2024, 25(13), 7139; https://doi.org/10.3390/ijms25137139 (registering DOI) - 28 Jun 2024
Abstract
Quorum sensing (QS) allows bacteria to coordinate their activities by producing and detecting low-molecular-weight signal molecules based on population density, thereby controlling the infectivity of bacteria through various virulence factors. Quorum-sensing inhibition is a promising approach to tackle bacterial communication. Cyclodextrins (CDs) are
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Quorum sensing (QS) allows bacteria to coordinate their activities by producing and detecting low-molecular-weight signal molecules based on population density, thereby controlling the infectivity of bacteria through various virulence factors. Quorum-sensing inhibition is a promising approach to tackle bacterial communication. Cyclodextrins (CDs) are a class of cyclic oligosaccharides that reversibly encapsulate the acyl chain of the signal molecules, thereby preventing their binding to receptors and interrupting bacterial communication. This results in the inhibition of the expression of various properties, including different virulence factors. To examine the potential quorum-quenching (QQ) ability of newly prepared cyclodextrin derivatives, we conducted short-term tests using Aliivibrio fischeri, a heterotrophic marine bacterium capable of bioluminescence controlled by quorum sensing. α- and β-cyclodextrins monosubstituted with alkylthio moieties and further derivatized with quaternary ammonium groups were used as the test agents. The effect of these cyclodextrins on the quorum-sensing system of A. fischeri was investigated by adding them to an exponential growth phase of the culture and then measuring bioluminescence intensity, population growth, and cell viability. Our results demonstrate that the tested cyclodextrins have an inhibitory effect on the quorum-sensing system of A. fischeri. The inhibitory effect varies based on the length of the alkyl chain, with alkylthio substitution enhancing it and the presence of quaternary ammonium groups decreasing it. Our findings suggest that cyclodextrins can be a promising therapeutic agent for the treatment of bacterial infections.
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(This article belongs to the Special Issue A Commemorative Issue in Honor of József Szejtli: Advances in Cyclodextrin Chemistry and Its Applications)
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The Effect of Conjugated Nitrile Structures as Acceptor Moieties on the Photovoltaic Properties of Dye-Sensitized Solar Cells: DFT and TD-DFT Investigation
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Maha J. Tommalieh, Abdulaziz I. Aljameel, Rageh K. Hussein, Khalled Al-heuseen, Suzan K. Alghamdi and Sharif Abu Alrub
Int. J. Mol. Sci. 2024, 25(13), 7138; https://doi.org/10.3390/ijms25137138 (registering DOI) - 28 Jun 2024
Abstract
A major challenge in improving the overall efficiency of dye-sensitized solar cells is improving the optoelectronic properties of small molecule acceptors. This work primarily investigated the effects of conjugation in nitriles incorporated as acceptor moieties into a newly designed series of D-A-A dyes.
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A major challenge in improving the overall efficiency of dye-sensitized solar cells is improving the optoelectronic properties of small molecule acceptors. This work primarily investigated the effects of conjugation in nitriles incorporated as acceptor moieties into a newly designed series of D-A-A dyes. Density functional theory was employed to specifically study how single–double and single–triple conjugation in nitriles alters the optical and electronic properties of these dyes. The Cy-4c dye with a highly conjugated nitrile unit attained the smallest band gap (1.80 eV), even smaller than that of the strong cyanacrylic anchor group (2.07 eV). The dyes lacking conjugation in nitrile groups did not contribute to the LUMO, while LUMOs extended from donors to conjugated nitrile components, facilitating intramolecular charge transfer and causing a strong bind to the film surface. Density of state analysis revealed a considerable impact of conjugated nitrile on the electronic properties of dyes through an effective contribution in the LUMO, exceeding the role of the well-known strong 2,1,3-benzothiadiazole acceptor unit. The excited state properties and the absorption spectra were investigated using time-dependent density functional theory (TD-DFT). Conjugation in the nitrile unit caused the absorption band to broaden, strengthen, and shift toward the near-infrared region. The proposed dyes also showed optimum photovoltaic properties; all dyes possess high light-harvesting efficiency (LHE) values, specifically 96% for the dyes Cy-3b and Cy-4c, which had the most conjugated nitrile moieties. The dyes with higher degrees of conjugation had longer excitation lifetime values, which promote charge transfer by causing steady charge recombination at the interface. These findings may provide new insights into the structure of conjugated nitriles and their function as acceptor moieties in DSSCS, which may lead to the development of extremely effective photosensitizers for solar cells.
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(This article belongs to the Special Issue Molecular Scale Studies of Computational Catalysis and Density Functional Theory in Materials Chemistry)
Open AccessArticle
Cutaneous Wound Healing and the Effects of Cannabidiol
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Pearl Shah, Kathryne Holmes, Fairouz Chibane, Phillip Wang, Pablo Chagas, Evila Salles, Melanie Jones, Patrick Palines, Mohamad Masoumy, Babak Baban and Jack Yu
Int. J. Mol. Sci. 2024, 25(13), 7137; https://doi.org/10.3390/ijms25137137 (registering DOI) - 28 Jun 2024
Abstract
Cutaneous wounds, both acute and chronic, begin with loss of the integrity, and thus barrier function, of the skin. Surgery and trauma produce acute wounds. There are 22 million surgical procedures per year in the United States alone, based on data from the
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Cutaneous wounds, both acute and chronic, begin with loss of the integrity, and thus barrier function, of the skin. Surgery and trauma produce acute wounds. There are 22 million surgical procedures per year in the United States alone, based on data from the American College of Surgeons, resulting in a prevalence of 6.67%. Acute traumatic wounds requiring repair total 8 million per year, 2.42% or 24.2 per 1000. The cost of wound care is increasing; it approached USD 100 billion for just Medicare in 2018. This burden for wound care will continue to rise with population aging, the increase in metabolic syndrome, and more elective surgeries. To heal a wound, an orchestrated, evolutionarily conserved, and complex series of events involving cellular and molecular agents at the local and systemic levels are necessary. The principal factors of this important function include elements from the neurological, cardiovascular, immune, nutritional, and endocrine systems. The objectives of this review are to provide clinicians engaged in wound care and basic science researchers interested in wound healing with an updated synopsis from recent publications. We also present data from our primary investigations, testing the hypothesis that cannabidiol can alter cutaneous wound healing and documenting their effects in wild type (C57/BL6) and db/db mice (Type 2 Diabetes Mellitus, T2DM). The focus is on the potential roles of the endocannabinoid system, cannabidiol, and the important immune-regulatory wound cytokine IL-33, a member of the IL-1 family, and connective tissue growth factor, CTGF, due to their roles in both normal and abnormal wound healing. We found an initial delay in the rate of wound closure in B6 mice with CBD, but this difference disappeared with time. CBD decreased IL-33 + cells in B6 by 70% while nearly increasing CTGF + cells in db/db mice by two folds from 18.6% to 38.8% (p < 0.05) using a dorsal wound model. We review the current literature on normal and abnormal wound healing, and document effects of CBD in B6 and db/db dorsal cutaneous wounds. CBD may have some beneficial effects in diabetic wounds. We applied 6–mm circular punch to create standard size full-thickness dorsal wounds in B6 and db/db mice. The experimental group received CBD while the control group got only vehicle. The outcome measures were rate of wound closure, wound cells expressing IL-33 and CTGF, and ILC profiles. In B6, the initial rate of wound closure was slower but there was no delay in the time to final closure, and cells expressing IL-33 was significantly reduced. CTGF + cells were higher in db/bd wounds treated with CBD. These data support the potential use of CBD to improve diabetic cutaneous wound healing.
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(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Open AccessArticle
Anti-Neuroinflammatory Effects of a Novel Bile Acid Derivative
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Srđan Bjedov, Goran Stegnjaić, Suzana Stanisavljević, Milica Lazarević, Ivan Pilipović, Marija Sakač and Đorđe Miljković
Int. J. Mol. Sci. 2024, 25(13), 7136; https://doi.org/10.3390/ijms25137136 (registering DOI) - 28 Jun 2024
Abstract
In the search for novel potent immunomodulatory nuclear factor-erythroid 2 related factor 2 (Nrf2) activators, a derivative of cholic bile acid, SB140, was synthesized. The synthesis of SB140 aimed to increase the electrophilic functionality of the compound, enhancing its ability to activate Nrf2.
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In the search for novel potent immunomodulatory nuclear factor-erythroid 2 related factor 2 (Nrf2) activators, a derivative of cholic bile acid, SB140, was synthesized. The synthesis of SB140 aimed to increase the electrophilic functionality of the compound, enhancing its ability to activate Nrf2. Effects of SB140 on microglial cells, myeloid-derived cells (MDC), and T cells were explored in the context of (central nervous system) CNS autoimmunity. SB140 potently activated Nrf2 signaling in MDC and microglia. It was efficient in reducing the ability of microglial cells to produce inflammatory nitric oxide, interleukin (IL)-6, and tumor necrosis factor (TNF). Also, SB140 reduced the proliferation of encephalitogenic T cells and the production of their effector cytokines: IL-17 and interferon (IFN)-γ. On the contrary, the effects of SB140 on anti-inflammatory IL-10 production in microglial and encephalitogenic T cells were limited or absent. These results show that SB140 is a potent Nrf2 activator, as well as an immunomodulatory compound. Thus, further research on the application of SB140 in the treatment of neuroinflammatory diseases is warranted. Animal models of multiple sclerosis and other inflammatory neurological disorders will be a suitable choice for such studies.
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(This article belongs to the Special Issue Editorial Board Members’ Collection Series: “Neuroinflammation”)
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Broncho-Vaxom Attenuates Lipopolysaccharide-Induced Inflammation in a Mouse Model of Acute Lung Injury
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Min-Seok Woo, Dang Long Cao, Eun-Jin Kim, Yi Yeong Jeong and Dawon Kang
Int. J. Mol. Sci. 2024, 25(13), 7135; https://doi.org/10.3390/ijms25137135 (registering DOI) - 28 Jun 2024
Abstract
Acute lung injury (ALI) is a condition associated with acute respiratory failure, resulting in significant morbidity and mortality. It involves cellular changes such as disruption of the alveolar–capillary membrane, excessive neutrophil migration, and release of inflammatory mediators. Broncho-Vaxom® (BV), a lyophilized product
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Acute lung injury (ALI) is a condition associated with acute respiratory failure, resulting in significant morbidity and mortality. It involves cellular changes such as disruption of the alveolar–capillary membrane, excessive neutrophil migration, and release of inflammatory mediators. Broncho-Vaxom® (BV), a lyophilized product containing cell membrane components derived from eight bacteria commonly found in the respiratory tract, is known for its potential to reduce viral and bacterial lung infections. However, the specific effect of BV on ALI has not been clearly defined. This study explored the preventive effects of BV and its underlying mechanisms in a lipopolysaccharide (LPS)-induced ALI mouse model. Oral BV (1 mg/kg) gavage was administered one hour before the intratracheal injection of LPS to evaluate its preventive effect on the ALI model. The pre-administration of BV significantly mitigates inflammatory parameters, including the production of inflammatory mediators, macrophage infiltration, and NF-κB activation in lung tissue, and the increase in inflammatory cells in bronchoalveolar lavage fluid (BALF). Moreover, BV (3 μg/mL) pretreatment reduced the expression of M1 macrophage markers, interleukins (IL-1β, IL-6), tumor necrosis factor α, and cyclooxygenase-2, which are activated by LPS, in both mouse alveolar macrophage MH-S cells and human macrophage THP-1 cells. These findings showed that BV exhibits anti-inflammatory effects by suppressing inflammatory mediators through the NF-κB pathway, suggesting its potential to attenuate bronchial and pulmonary inflammation.
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(This article belongs to the Special Issue Inflammatory Airway Diseases: Diagnosis, Pathology, Molecular Mechanisms and Treatment Options)