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
Poor Decision Making and Sociability Impairment Following Central Serotonin Reduction in Inducible TPH2-Knockdown Rats
Int. J. Mol. Sci. 2024, 25(9), 5003; https://doi.org/10.3390/ijms25095003 (registering DOI) - 03 May 2024
Abstract
Serotonin is an essential neuromodulator for mental health and animals’ socio-cognitive abilities. However, we previously found that a constitutive depletion of central serotonin did not impair rat cognitive abilities in stand-alone tests. Here, we investigated how a mild and acute decrease in brain
[...] Read more.
Serotonin is an essential neuromodulator for mental health and animals’ socio-cognitive abilities. However, we previously found that a constitutive depletion of central serotonin did not impair rat cognitive abilities in stand-alone tests. Here, we investigated how a mild and acute decrease in brain serotonin would affect rats’ cognitive abilities. Using a novel rat model of inducible serotonin depletion via the genetic knockdown of tryptophan hydroxylase 2 (TPH2), we achieved a 20% decrease in serotonin levels in the hypothalamus after three weeks of non-invasive oral doxycycline administration. Decision making, cognitive flexibility, and social recognition memory were tested in low-serotonin (Tph2-kd) and control rats. Our results showed that the Tph2-kd rats were more prone to choose disadvantageously in the long term (poor decision making) in the Rat Gambling Task and that only the low-serotonin poor decision makers were more sensitive to probabilistic discounting and had poorer social recognition memory than other low-serotonin and control individuals. Flexibility was unaffected by the acute brain serotonin reduction. Poor social recognition memory was the most central characteristic of the behavioral network of low-serotonin poor decision makers, suggesting a key role of social recognition in the expression of their profile. The acute decrease in brain serotonin appeared to specifically amplify the cognitive impairments of the subgroup of individuals also identified as poor decision makers in the population. This study highlights the great opportunity the Tph2-kd rat model offers to study inter-individual susceptibilities to develop cognitive impairment following mild variations of brain serotonin in otherwise healthy individuals. These transgenic and differential approaches together could be critical for the identification of translational markers and vulnerabilities in the development of mental disorders.
Full article
(This article belongs to the Special Issue Neuromodulatory Effects of Serotonin)
►
Show Figures
Open AccessArticle
Lytic and Latent Genetic Diversity of the Epstein–Barr Virus Reveals Raji-Related Variants from Southeastern Brazil Associated with Recombination Markers
by
Paula D. Alves, Paulo Rohan, Rocio Hassan and Eliana Abdelhay
Int. J. Mol. Sci. 2024, 25(9), 5002; https://doi.org/10.3390/ijms25095002 (registering DOI) - 03 May 2024
Abstract
Epstein–Barr virus (EBV) is a ubiquitous gammaherpesvirus etiologically associated with benign and malignant diseases. Since the pathogenic mechanisms of EBV are not fully understood, understanding EBV genetic diversity is an ongoing goal. Therefore, the present work describes the genetic diversity of the lytic
[...] Read more.
Epstein–Barr virus (EBV) is a ubiquitous gammaherpesvirus etiologically associated with benign and malignant diseases. Since the pathogenic mechanisms of EBV are not fully understood, understanding EBV genetic diversity is an ongoing goal. Therefore, the present work describes the genetic diversity of the lytic gene BZLF1 in a sampling of 70 EBV-positive cases from southeastern Brazil. Additionally, together with the genetic regions previously characterized, the aim of the present study was to determine the impact of viral genetic factors that may influence EBV genetic diversity. Accordingly, the phylogenetic analysis of the BZLF1 indicated two main clades with high support, BZ-A and BZ-B (PP > 0.85). Thus, the BZ-A clade was the most diverse clade associated with the main polymorphisms investigated, including the haplotype Type 1 + V3 (p < 0.001). Furthermore, the multigene phylogenetic analysis (MLA) between BZLF1 and the oncogene LMP1 showed specific clusters, revealing haplotypic segregation that previous single-gene phylogenies from both genes failed to demonstrate. Surprisingly, the LMP1 Raji-related variant clusters were shown to be more diverse, associated with BZ-A/B and the Type 2/1 + V3 haplotypes. Finally, due to the high haplotypic diversity of the Raji-related variants, the number of DNA recombination-inducing motifs (DRIMs) was evaluated within the different clusters defined by the MLA. Similarly, the haplotype BZ-A + Raji was shown to harbor a greater number of DRIMs (p < 0.001). These results call attention to the high haplotype diversity of EBV in southeast Brazil and strengthen the hypothesis of the recombinant potential of South American Raji-related variants via the LMP1 oncogene.
Full article
(This article belongs to the Special Issue Recent Advances in Herpesviruses)
►▼
Show Figures
Figure 1
Open AccessReview
The Role of Inflammasome in Abdominal Aortic Aneurysm and Its Potential Drugs
by
Suyu Pi, Sizheng Xiong, Yan Yuan and Hongping Deng
Int. J. Mol. Sci. 2024, 25(9), 5001; https://doi.org/10.3390/ijms25095001 (registering DOI) - 03 May 2024
Abstract
Abdominal aortic aneurysm (AAA) has been recognized as a serious chronic inflammatory degenerative aortic disease in recent years. At present, there is no other effective intervention except surgical treatment for AAA. With the aging of the human population, its incidence is increasing year
[...] Read more.
Abdominal aortic aneurysm (AAA) has been recognized as a serious chronic inflammatory degenerative aortic disease in recent years. At present, there is no other effective intervention except surgical treatment for AAA. With the aging of the human population, its incidence is increasing year by year, posing a serious threat to human health. Modern studies suggest that vascular chronic inflammatory response is the core process in AAA occurrence and development. Inflammasome, a multiprotein complex located in the cytoplasm, mediates the expression of various inflammatory cytokines like interleukin (IL)-1β and IL-18, and thus plays a pivotal role in inflammation regulation. Therefore, inflammasome may exert a crucial influence on the progression of AAA. This article reviews some mechanism studies to investigate the role of inflammasome in AAA and then summarizes several potential drugs targeting inflammasome for the treatment of AAA, aiming to provide new ideas for the clinical prevention and treatment of AAA beyond surgical methods.
Full article
(This article belongs to the Special Issue Cardiovascular Diseases: Molecular Mechanisms and Potential Therapy)
►▼
Show Figures
Figure 1
Open AccessArticle
Optoelectronic Response to the Fluor Ion Bond on 4-(4,4,5,5-Tetramethyl-1,3,2-dioxoborolan-2-yl)benzaldehyde
by
Ulises J. Guevara, Jesús Núñez, Laura M. Pérez, Anton Tiutiunnyk, Neudo Urdaneta, Eduardo Cisternas and David Laroze
Int. J. Mol. Sci. 2024, 25(9), 5000; https://doi.org/10.3390/ijms25095000 (registering DOI) - 03 May 2024
Abstract
Boronate esters are a class of compounds containing a boron atom bonded to two oxygen atoms in an ester group, often being used as precursors in the synthesis of other materials. The characterization of the structure and properties of esters is usually carried
[...] Read more.
Boronate esters are a class of compounds containing a boron atom bonded to two oxygen atoms in an ester group, often being used as precursors in the synthesis of other materials. The characterization of the structure and properties of esters is usually carried out by UV-visible, infrared, and nuclear magnetic resonance (NMR) spectroscopic techniques. With the aim to better understand our experimental data, in this article, the density functional theory (DFT) is used to analyze the UV-visible and infrared spectra, as well as the isotropic shielding and chemical shifts of the hydrogen atoms H, carbon C and boron B in the compound 4-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)benzaldehyde. Furthermore, this study considers the change in its electronic and spectroscopic properties of this particular ester, when its boron atom is coordinated with a fluoride anion. The calculations were carried out using the LSDA and B3LYP functionals in Gaussian-16, and PBE in CASTEP. The results show that the B3LYP functional gives the best approximation to the experimental data. The formation of a coordinated covalent B–F bond highlights the remarkable sensitivity of the NMR chemical shifts of carbon, oxygen, and boron atoms and their surroundings. Furthermore, this bond also highlights the changes in the electron transitions bands and during the absorption and emission of a photon in the UV-vis, and in the stretching bands of the C=C bonds, and bending of BO in the infrared spectrum. This study not only contributes to the understanding of the properties of boronate esters but also provides important information on the interactions and responses optoelectronic of the compound when is bonded to a fluorine atom.
Full article
(This article belongs to the Special Issue Application of Nuclear Magnetic Resonance (NMR) Spectroscopy in Bioorganic Chemistry)
Open AccessArticle
Microbial Polysaccharides Extracted from Different Mature Muds of the Euganean Thermal District Show Similar Anti-Inflammatory Activity In Vivo
by
Micol Caichiolo, Raffaella Margherita Zampieri, Alessandra Adessi, Matilde Ciani, Fabrizio Caldara, Luisa Dalla Valle and Nicoletta La Rocca
Int. J. Mol. Sci. 2024, 25(9), 4999; https://doi.org/10.3390/ijms25094999 (registering DOI) - 03 May 2024
Abstract
The Euganean Thermal District, situated in North-East Italy, is one of Europe’s largest and oldest thermal centres. The topical application of its therapeutic thermal muds is recognised by the Italian Health System as a beneficial treatment for patients suffering from arthro-rheumatic diseases. Polysaccharides
[...] Read more.
The Euganean Thermal District, situated in North-East Italy, is one of Europe’s largest and oldest thermal centres. The topical application of its therapeutic thermal muds is recognised by the Italian Health System as a beneficial treatment for patients suffering from arthro-rheumatic diseases. Polysaccharides produced by the mud microbiota have been recently identified as anti-inflammatory bioactive molecules. In this paper we analysed the efficacy of Microbial-Polysaccharides (M-PS) derived from mature muds obtained at different maturation temperatures, both within and outside the codified traditional mud maturation range. M-PSs were extracted from six mature muds produced by five spas of the Euganean Thermal District and investigated for their chemical properties, monosaccharide composition and in vivo anti-inflammatory potential, using the zebrafish model organism. Additionally, mature muds were characterized for their microbiota composition using Next-Generation Sequencing. The results showed that all M-PSs exhibit similar anti-inflammatory potential, referable to their comparable chemical composition. This consistency was observed despite changes in cyanobacteria populations, suggesting a possible role of the entire microbial community in shaping the properties of these biomolecules. These findings highlight the importance of scientific research in untangling the origins of the therapeutic efficacy of Euganean Thermal muds in the treatment of chronic inflammatory conditions.
Full article
(This article belongs to the Special Issue Investigation of Natural Products as Sources of Bioactive Molecules)
►▼
Show Figures
Figure 1
Open AccessArticle
Aspartate β-Hydroxylase Is Upregulated in Head and Neck Squamous Cell Carcinoma and Regulates Invasiveness in Cancer Cell Models
by
Pritha Mukherjee, Xin Zhou, Susana Galli, Bruce Davidson, Lihua Zhang, Jaeil Ahn, Reem Aljuhani, Julius Benicky, Laurie Ailles, Vitor H. Pomin, Mark Olsen and Radoslav Goldman
Int. J. Mol. Sci. 2024, 25(9), 4998; https://doi.org/10.3390/ijms25094998 (registering DOI) - 03 May 2024
Abstract
Aspartate β-hydroxylase (ASPH) is a protein associated with malignancy in a wide range of tumors. We hypothesize that inhibition of ASPH activity could have anti-tumor properties in patients with head and neck cancer. In this study, we screened tumor tissues of 155 head
[...] Read more.
Aspartate β-hydroxylase (ASPH) is a protein associated with malignancy in a wide range of tumors. We hypothesize that inhibition of ASPH activity could have anti-tumor properties in patients with head and neck cancer. In this study, we screened tumor tissues of 155 head and neck squamous cell carcinoma (HNSCC) patients for the expression of ASPH using immunohistochemistry. We used an ASPH inhibitor, MO-I-1151, known to inhibit the catalytic activity of ASPH in the endoplasmic reticulum, to show its inhibitory effect on the migration of SCC35 head and neck cancer cells in cell monolayers and in matrix-embedded spheroid co-cultures with primary cancer-associated fibroblast (CAF) CAF 61137 of head and neck origin. We also studied a combined effect of MO-I-1151 and HfFucCS, an inhibitor of invasion-blocking heparan 6-O-endosulfatase activity. We found ASPH was upregulated in HNSCC tumors compared to the adjacent normal tissues. ASPH was uniformly high in expression, irrespective of tumor stage. High expression of ASPH in tumors led us to consider it as a therapeutic target in cell line models. ASPH inhibitor MO-I-1151 had significant effects on reducing migration and invasion of head and neck cancer cells, both in monolayers and matrix-embedded spheroids. The combination of the two enzyme inhibitors showed an additive effect on restricting invasion in the HNSCC cell monolayers and in the CAF-containing co-culture spheroids. We identify ASPH as an abundant protein in HNSCC tumors. Targeting ASPH with inhibitor MO-I-1151 effectively reduces CAF-mediated cellular invasion in cancer cell models. We propose that the additive effect of MO-I-1151 with HfFucCS, an inhibitor of heparan 6-O-endosulfatases, on HNSCC cells could improve interventions and needs to be further explored.
Full article
(This article belongs to the Special Issue Pathogenesis and Treatments of Head and Neck Cancer)
Open AccessArticle
The Usefulness of Vitamin K-Dependent Proteins in the Diagnosis of Colorectal Carcinoma
by
Mirela-Georgiana Perné, Adela-Viviana Sitar-Tăut, Olga Hilda Orășan, Vasile Negrean, Călin Vasile Vlad, Teodora-Gabriela Alexescu, Mircea Vasile Milaciu, Lorena Ciumărnean, Răzvan Dan Togănel, Gabriel Emil Petre, Ioan Șimon and Alexandra Crăciun
Int. J. Mol. Sci. 2024, 25(9), 4997; https://doi.org/10.3390/ijms25094997 (registering DOI) - 03 May 2024
Abstract
Colorectal cancer (CRC) is one of the most common neoplasms in developed countries, with increasing incidence and mortality, even in young people. A variety of serum markers have been associated with CRC (CEA, CA 19-9), but neither should be used as a screening
[...] Read more.
Colorectal cancer (CRC) is one of the most common neoplasms in developed countries, with increasing incidence and mortality, even in young people. A variety of serum markers have been associated with CRC (CEA, CA 19-9), but neither should be used as a screening tool for the diagnosis or evolution staging of CRC. The sensitivity and specificity of these markers are not as good as is required, so new ones need to be found. Matrix Gla protein and PIVKA II are involved in carcinogenesis, but few studies have evaluated their usefulness in predicting the presence and severity of CRC. Materials and Methods: Two hundred patients were divided into three groups: 80 patients were included in the control group; 80 with CRC and without hepatic metastasis were included in Group 1; 40 patients with CRC and hepatic metastasis were included in Group 2. Vitamin K-dependent proteins (VKDPs) levels in plasma were determined. Results: Patients with CRC without methastasis (Group 1) and CRC patients with methastasis (Group 2) presented significantly higher values of CEA, CA 19-9, PIVKA II (310.05 ± 38.22 vs. 430.13 ± 122.13 vs. 20.23 ± 10.90), and ucMGP (14,300.00 ± 2387.02 vs. 13,410.52 ± 2243.16 vs. 1780.31 ± 864.70) compared to control group (Group 0). Interestingly, Group 1 presented the greatest PIVKA II values. Out of all the markers, significant differences between the histological subgroups were found only for ucMGP , but only in non-metastatic CRC. Studying the discrimination capacity between the patients with CRC vs. those without, no significant differences were found between the classical tumor markers and the VKDP AUROC curves (PIVKA II and ucMGP AUROCs = 1). For the metastatic stage, the sensitivity and specificity of the VKDPs were lower in comparison with those of CA 19-9 and CEA, respectively (PIVKA II AUROC = 0.789, ucMGP AUROC = 0.608). Conclusion: The serum levels of these VKDPs are significantly altered in patients with colorectal carcinoma; it is possible to find additional value of these in the early stages of the disease.
Full article
(This article belongs to the Special Issue New Diagnostic Tools and Biomarkers in Oncological Diseases 2.0)
Open AccessReview
An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis
by
Rita Pereira and Rui Bergantim
Int. J. Mol. Sci. 2024, 25(9), 4996; https://doi.org/10.3390/ijms25094996 (registering DOI) - 03 May 2024
Abstract
Multiple myeloma (MM), the second most common hematologic malignancy, remains incurable, and its incidence is rising. Chimeric Antigen Receptor T-cell (CAR-T cell) therapy has emerged as a novel treatment, with the potential to improve the survival and quality of life of patients with
[...] Read more.
Multiple myeloma (MM), the second most common hematologic malignancy, remains incurable, and its incidence is rising. Chimeric Antigen Receptor T-cell (CAR-T cell) therapy has emerged as a novel treatment, with the potential to improve the survival and quality of life of patients with relapsed/refractory multiple myeloma (rrMM). In this systematic review and meta-analysis, conducted in accordance with PRISMA guidelines, we aim to provide a concise overview of the latest developments in CAR-T therapy, assess their potential implications for clinical practice, and evaluate their efficacy and safety outcomes based on the most up-to-date evidence. A literature search conducted from 1 January 2019 to 12 July 2023 on Medline/PubMed, Scopus, and Web of Science identified 2273 articles, of which 29 fulfilled the specified criteria for inclusion. Our results offer robust evidence supporting CAR-T cell therapy’s efficacy in rrMM patients, with an encouraging 83.21% overall response rate (ORR). A generally safe profile was observed, with grade ≥ 3 cytokine release syndrome (CRS) at 7.12% and grade ≥ 3 neurotoxicity at 1.37%. A subgroup analysis revealed a significantly increased ORR in patients with fewer antimyeloma regimens, while grade ≥ 3 CRS was more common in those with a higher proportion of high-risk cytogenetics and prior exposure to BCMA therapy.
Full article
(This article belongs to the Special Issue Recent Advances in Immunotherapy of Multiple Myeloma)
►▼
Show Figures
Figure 1
Open AccessReview
Unraveling the Connection: Pain and Endoplasmic Reticulum Stress
by
Ryoko Kawanaka, Hisayo Jin and Tomohiko Aoe
Int. J. Mol. Sci. 2024, 25(9), 4995; https://doi.org/10.3390/ijms25094995 (registering DOI) - 03 May 2024
Abstract
Pain is a complex and multifaceted experience. Recent research has increasingly focused on the role of endoplasmic reticulum (ER) stress in the induction and modulation of pain. The ER is an essential organelle for cells and plays a key role in protein folding
[...] Read more.
Pain is a complex and multifaceted experience. Recent research has increasingly focused on the role of endoplasmic reticulum (ER) stress in the induction and modulation of pain. The ER is an essential organelle for cells and plays a key role in protein folding and calcium dynamics. Various pathological conditions, such as ischemia, hypoxia, toxic substances, and increased protein production, may disturb protein folding, causing an increase in misfolding proteins in the ER. Such an overload of the folding process leads to ER stress and causes the unfolded protein response (UPR), which increases folding capacity in the ER. Uncompensated ER stress impairs intracellular signaling and cell function, resulting in various diseases, such as diabetes and degenerative neurological diseases. ER stress may be a critical universal mechanism underlying human diseases. Pain sensations involve the central as well as peripheral nervous systems. Several preclinical studies indicate that ER stress in the nervous system is enhanced in various painful states, especially in neuropathic pain conditions. The purpose of this narrative review is to uncover the intricate relationship between ER stress and pain, exploring molecular pathways, implications for various pain conditions, and potential therapeutic strategies.
Full article
(This article belongs to the Special Issue Protein Quality Control and Integrated Stress Response Related to Pain Disorders)
Open AccessArticle
Unraveling the Mechanisms Involved in the Beneficial Effects of Magnesium Treatment on Skin Wound Healing
by
Yuta Yoshino, Tatsuki Teruya, Chika Miyamoto, Mai Hirose, Satoshi Endo and Akira Ikari
Int. J. Mol. Sci. 2024, 25(9), 4994; https://doi.org/10.3390/ijms25094994 (registering DOI) - 03 May 2024
Abstract
The skin wound healing process consists of hemostatic, inflammatory, proliferative, and maturation phases, with a complex cellular response by multiple cell types in the epidermis, dermis, and immune system. Magnesium is a mineral essential for life, and although magnesium treatment promotes cutaneous wound
[...] Read more.
The skin wound healing process consists of hemostatic, inflammatory, proliferative, and maturation phases, with a complex cellular response by multiple cell types in the epidermis, dermis, and immune system. Magnesium is a mineral essential for life, and although magnesium treatment promotes cutaneous wound healing, the molecular mechanism and timing of action of the healing process are unknown. This study, using human epidermal-derived HaCaT cells and human normal epidermal keratinocyte cells, was performed to investigate the mechanism involved in the effect of magnesium on wound healing. The expression levels of epidermal differentiation-promoting factors were reduced by MgCl2, suggesting an inhibitory effect on epidermal differentiation in the remodeling stage of the late wound healing process. On the other hand, MgCl2 treatment increased the expression of matrix metalloproteinase-7 (MMP7), a cell migration-promoting factor, and enhanced cell migration via the MEK/ERK pathway activation. The enhancement of cell migration by MgCl2 was inhibited by MMP7 knockdown, suggesting that MgCl2 enhances cell migration which is mediated by increased MMP7 expression. Our results revealed that MgCl2 inhibits epidermal differentiation but promotes cell migration, suggesting that applying magnesium to the early wound healing process could be beneficial.
Full article
(This article belongs to the Special Issue The Role of Mg Homeostasis in Disease)
►▼
Show Figures
Figure 1
Open AccessArticle
KCTD Proteins Have Redundant Functions in Controlling Cellular Growth
by
Robert Rizk, Dominic Devost, Darlaine Pétrin and Terence E. Hébert
Int. J. Mol. Sci. 2024, 25(9), 4993; https://doi.org/10.3390/ijms25094993 (registering DOI) - 03 May 2024
Abstract
We explored the functional redundancy of three structurally related KCTD (Potassium Channel Tetramerization Domain) proteins, KCTD2, KCTD5, and KCTD17, by progressively knocking them out in HEK 293 cells using CRISPR/Cas9 genome editing. After validating the knockout, we assessed the effects of progressive knockout
[...] Read more.
We explored the functional redundancy of three structurally related KCTD (Potassium Channel Tetramerization Domain) proteins, KCTD2, KCTD5, and KCTD17, by progressively knocking them out in HEK 293 cells using CRISPR/Cas9 genome editing. After validating the knockout, we assessed the effects of progressive knockout on cell growth and gene expression. We noted that the progressive effects of knockout of KCTD isoforms on cell growth were most pervasive when all three isoforms were deleted, suggesting some functions were conserved between them. This was also reflected in progressive changes in gene expression. Our previous work indicated that Gβ1 was involved in the transcriptional control of gene expression, so we compared the gene expression patterns between GNB1 and KCTD KO. Knockout of GNB1 led to numerous changes in the expression levels of other G protein subunit genes, while knockout of KCTD isoforms had the opposite effect, presumably because of their role in regulating levels of Gβ1. Our work demonstrates a unique relationship between KCTD proteins and Gβ1 and a global role for this subfamily of KCTD proteins in maintaining the ability of cells to survive and proliferate.
Full article
(This article belongs to the Special Issue Roles of KCTD Proteins in Biological Processes and Diseases: State of the Art and Future Perspectives)
Open AccessArticle
Development of a Static Avascular and Dynamic Vascular Human Skin Equivalent Employing Collagen/Keratin Hydrogels
by
Kameel Zuniga, Neda Ghousifam, Lucy Shaffer, Sean Brocklehurst, Mark Van Dyke, Robert Christy, Shanmugasundaram Natesan and Marissa Nichole Rylander
Int. J. Mol. Sci. 2024, 25(9), 4992; https://doi.org/10.3390/ijms25094992 - 03 May 2024
Abstract
One of the primary complications in generating physiologically representative skin tissue is the inability to integrate vasculature into the system, which has been shown to promote the proliferation of basal keratinocytes and consequent keratinocyte differentiation, and is necessary for mimicking representative barrier function
[...] Read more.
One of the primary complications in generating physiologically representative skin tissue is the inability to integrate vasculature into the system, which has been shown to promote the proliferation of basal keratinocytes and consequent keratinocyte differentiation, and is necessary for mimicking representative barrier function in the skin and physiological transport properties. We created a 3D vascularized human skin equivalent (VHSE) with a dermal and epidermal layer, and compared keratinocyte differentiation (immunomarker staining), epidermal thickness (H&E staining), and barrier function (transepithelial electrical resistance (TEER) and dextran permeability) to a static, organotypic avascular HSE (AHSE). The VHSE had a significantly thicker epidermal layer and increased resistance, both an indication of increased barrier function, compared to the AHSE. The inclusion of keratin in our collagen hydrogel extracellular matrix (ECM) increased keratinocyte differentiation and barrier function, indicated by greater resistance and decreased permeability. Surprisingly, however, endothelial cells grown in a collagen/keratin extracellular environment showed increased cell growth and decreased vascular permeability, indicating a more confluent and tighter vessel compared to those grown in a pure collagen environment. The development of a novel VHSE, which incorporated physiological vasculature and a unique collagen/keratin ECM, improved barrier function, vessel development, and skin structure compared to a static AHSE model.
Full article
(This article belongs to the Special Issue Research Progress on 3D Cultures for Modeling the Microenvironment)
►▼
Show Figures
Figure 1
Open AccessArticle
Influence of Cold Stress on Physiological and Phytochemical Characteristics and Secondary Metabolite Accumulation in Microclones of Juglans regia L.
by
Nina V. Terletskaya, Elvira A. Shadenova, Yuliya A. Litvinenko, Kazhybek Ashimuly, Malika Erbay, Aigerim Mamirova, Irada Nazarova, Nataliya D. Meduntseva, Nataliya O. Kudrina, Nazym K. Korbozova and Erika D. Djangalina
Int. J. Mol. Sci. 2024, 25(9), 4991; https://doi.org/10.3390/ijms25094991 - 03 May 2024
Abstract
The current study investigated the impact of cold stress on the morphological, physiological, and phytochemical properties of Juglans regia L. (J. regia) using in vitro microclone cultures. The study revealed significant stress-induced changes in the production of secondary antioxidant metabolites. According
[...] Read more.
The current study investigated the impact of cold stress on the morphological, physiological, and phytochemical properties of Juglans regia L. (J. regia) using in vitro microclone cultures. The study revealed significant stress-induced changes in the production of secondary antioxidant metabolites. According to gas chromatography–mass spectrometry (GC–MS) analyses, the stress conditions profoundly altered the metabolism of J. regia microclones. Although the overall spectrum of metabolites was reduced, the production of key secondary antioxidant metabolites significantly increased. Notably, there was a sevenfold (7×) increase in juglone concentration. These findings are crucial for advancing walnut metabolomics and enhancing our understanding of plant responses to abiotic stress factors. Additionally, study results aid in identifying the role of individual metabolites in these processes, which is essential for developing strategies to improve plant resilience and tolerance to adverse conditions.
Full article
(This article belongs to the Special Issue Recent Analysis and Applications of Mass Spectrum in Biochemistry 2.0)
►▼
Show Figures
Figure 1
Open AccessArticle
Predicting Transcription Factor Binding Sites with Deep Learning
by
Nimisha Ghosh, Daniele Santoni, Indrajit Saha and Giovanni Felici
Int. J. Mol. Sci. 2024, 25(9), 4990; https://doi.org/10.3390/ijms25094990 - 03 May 2024
Abstract
Prediction of binding sites for transcription factors is important to understand how the latter regulate gene expression and how this regulation can be modulated for therapeutic purposes. A consistent number of references address this issue with different approaches, Machine Learning being one of
[...] Read more.
Prediction of binding sites for transcription factors is important to understand how the latter regulate gene expression and how this regulation can be modulated for therapeutic purposes. A consistent number of references address this issue with different approaches, Machine Learning being one of the most successful. Nevertheless, we note that many such approaches fail to propose a robust and meaningful method to embed the genetic data under analysis. We try to overcome this problem by proposing a bidirectional transformer-based encoder, empowered by bidirectional long-short term memory layers and with a capsule layer responsible for the final prediction. To evaluate the efficiency of the proposed approach, we use benchmark ChIP-seq datasets of five cell lines available in the ENCODE repository (A549, GM12878, Hep-G2, H1-hESC, and Hela). The results show that the proposed method can predict TFBS within the five different cell lines very well; moreover, cross-cell predictions provide satisfactory results as well. Experiments conducted across cell lines are reinforced by the analysis of five additional lines used only to test the model trained using the others. The results confirm that prediction across cell lines remains very high, allowing an extensive cross-transcription factor analysis to be performed from which several indications of interest for molecular biology may be drawn.
Full article
(This article belongs to the Special Issue Deep Learning in Bioinformatics and Biological Data Analysis)
►▼
Show Figures
Figure 1
Open AccessArticle
Exploring CDKN1A Upregulation Mechanisms: Insights into Cell Cycle Arrest Induced by NC2603 Curcumin Analog in MCF-7 Breast Cancer Cells
by
Felipe Garcia Nishimura, Beatriz Borsani Sampaio, Tatiana Takahasi Komoto, Wanessa Julia da Silva, Mariana Mezencio Gregório da Costa, Gabriela Inforçatti Haddad, Kamila Chagas Peronni, Adriane Feijó Evangelista, Mohammad Hossain, Jonathan R. Dimmock, Brian Bandy, Rene Oliveira Beleboni, Mozart Marins and Ana Lucia Fachin
Int. J. Mol. Sci. 2024, 25(9), 4989; https://doi.org/10.3390/ijms25094989 - 03 May 2024
Abstract
Breast cancer stands out as one of the most prevalent malignancies worldwide, necessitating a nuanced understanding of its molecular underpinnings for effective treatment. Hormone receptors in breast cancer cells substantially influence treatment strategies, dictating therapeutic approaches in clinical settings, serving as a guide
[...] Read more.
Breast cancer stands out as one of the most prevalent malignancies worldwide, necessitating a nuanced understanding of its molecular underpinnings for effective treatment. Hormone receptors in breast cancer cells substantially influence treatment strategies, dictating therapeutic approaches in clinical settings, serving as a guide for drug development, and aiming to enhance treatment specificity and efficacy. Natural compounds, such as curcumin, offer a diverse array of chemical structures with promising therapeutic potential. Despite curcumin’s benefits, challenges like poor solubility and rapid metabolism have spurred the exploration of analogs. Here, we evaluated the efficacy of the curcumin analog NC2603 to induce cell cycle arrest in MCF-7 breast cancer cells and explored its molecular mechanisms. Our findings reveal potent inhibition of cell viability (IC50 = 5.6 μM) and greater specificity than doxorubicin toward MCF-7 vs. non-cancer HaCaT cells. Transcriptome analysis identified 12,055 modulated genes, most notably upregulation of GADD45A and downregulation of ESR1, implicating CDKN1A-mediated regulation of proliferation and cell cycle genes. We hypothesize that the curcumin analog by inducing GADD45A expression and repressing ESR1, triggers the expression of CDKN1A, which in turn downregulates the expression of many important genes of proliferation and the cell cycle. These insights advance our understanding of curcumin analogs’ therapeutic potential, highlighting not just their role in treatment, but also the molecular pathways involved in their activity toward breast cancer cells.
Full article
(This article belongs to the Special Issue Molecular Mechanisms and New Therapies for Breast Cancer)
►▼
Show Figures
Figure 1
Open AccessEditorial
Molecular Insight of Plants Response to Drought Stress: Perspectives and New Insights towards Food Security
by
Isabel Marques and Honghong Hu
Int. J. Mol. Sci. 2024, 25(9), 4988; https://doi.org/10.3390/ijms25094988 (registering DOI) - 03 May 2024
Abstract
In the face of climate-induced challenges, understanding the intricate molecular mechanisms underlying drought tolerance in plants has become imperative [...]
Full article
(This article belongs to the Special Issue Molecular Insight of Plants Response to Drought Stress)
Open AccessArticle
Podocyte-Specific Deletion of MCP-1 Fails to Protect against Angiotensin II- or Adriamycin-Induced Glomerular Disease
by
Corry D. Bondi, Hannah L. Hartman, Brittney M. Rush and Roderick J. Tan
Int. J. Mol. Sci. 2024, 25(9), 4987; https://doi.org/10.3390/ijms25094987 (registering DOI) - 03 May 2024
Abstract
Investigating the role of podocytes in proteinuric disease is imperative to address the increasing global burden of chronic kidney disease (CKD). Studies strongly implicate increased levels of monocyte chemoattractant protein-1 (MCP-1/CCL2) in proteinuric CKD. Since podocytes express the receptor for MCP-1 (i.e., CCR2),
[...] Read more.
Investigating the role of podocytes in proteinuric disease is imperative to address the increasing global burden of chronic kidney disease (CKD). Studies strongly implicate increased levels of monocyte chemoattractant protein-1 (MCP-1/CCL2) in proteinuric CKD. Since podocytes express the receptor for MCP-1 (i.e., CCR2), we hypothesized that podocyte-specific MCP-1 production in response to stimuli could activate its receptor in an autocrine manner, leading to further podocyte injury. To test this hypothesis, we generated podocyte-specific MCP-1 knockout mice (Podo-Mcp-1fl/fl) and exposed them to proteinuric injury induced by either angiotensin II (Ang II; 1.5 mg/kg/d, osmotic minipump) or Adriamycin (Adr; 18 mg/kg, intravenous bolus). At baseline, there were no between-group differences in body weight, histology, albuminuria, and podocyte markers. After 28 days, there were no between-group differences in survival, change in body weight, albuminuria, kidney function, glomerular injury, and tubulointerstitial fibrosis. The lack of protection in the knockout mice suggests that podocyte-specific MCP-1 production is not a major contributor to either Ang II- or Adr-induced glomerular disease, implicating that another cell type is the source of pathogenic MCP-1 production in CKD.
Full article
(This article belongs to the Section Molecular Biology)
►▼
Show Figures
Figure 1
Open AccessArticle
The Role of Glutathione Transferase Omega-Class Variant Alleles in Individual Susceptibility to Ovarian Cancer
by
Petar Simic, Vesna Coric, Igor Pljesa, Ana Savic-Radojevic, Nebojsa Zecevic, Jovana Kocic, Tatjana Simic, Vladimir Pazin and Marija Pljesa-Ercegovac
Int. J. Mol. Sci. 2024, 25(9), 4986; https://doi.org/10.3390/ijms25094986 - 03 May 2024
Abstract
The tumor microenvironment is affected by reactive oxygen species and has been suggested to have an important role in ovarian cancer (OC) tumorigenesis. The role of glutathione transferases (GSTs) in the maintenance of redox balance is considered as an important contributing factor in
[...] Read more.
The tumor microenvironment is affected by reactive oxygen species and has been suggested to have an important role in ovarian cancer (OC) tumorigenesis. The role of glutathione transferases (GSTs) in the maintenance of redox balance is considered as an important contributing factor in cancer, including OC. Furthermore, GSTs are mostly encoded by highly polymorphic genes, which further highlights their potential role in OC, known to originate from accumulated genetic changes. Since the potential relevance of genetic variations in omega-class GSTs (GSTO1 and GSTO2), with somewhat different activities such as thioltransferase and dehydroascorbate reductase activity, has not been clarified as yet in terms of susceptibility to OC, we aimed to investigate whether the presence of different GSTO1 and GSTO2 genetic variants, individually or combined, might represent determinants of risk for OC development. Genotyping was performed in 110 OC patients and 129 matched controls using a PCR-based assay for genotyping single nucleotide polymorphisms. The results of our study show that homozygous carriers of the GSTO2 variant G allele are at an increased risk of OC development in comparison to the carriers of the referent genotype (OR1 = 2.16, 95% CI: 0.88–5.26, p = 0.08; OR2 = 2.49, 95% CI: 0.93–6.61, p = 0.06). Furthermore, individuals with GST omega haplotype H2, meaning the concomitant presence of the GSTO1*A and GSTO2*G alleles, are more susceptible to OC development, while carriers of the H4 (*A*A) haplotype exhibited lower risk of OC when crude and adjusted haplotype analysis was performed (OR1 = 0.29; 95% CI: 0.12–0.70; p = 0.007 and OR2 = 0.27; 95% CI: 0.11–0.67; p = 0.0054). Overall, our results suggest that GSTO locus variants may confer OC risk.
Full article
(This article belongs to the Special Issue Gynecologic Cancer: From Molecular, Cellular Mechanisms to Novel Therapies)
►▼
Show Figures
Figure 1
Open AccessReview
Extreme Tolerance of Extraocular Muscles to Diseases and Aging: Why and How?
by
Angelina Titova, Sergey Nikolaev, Airat Bilyalov, Nikita Filatov, Sergei Brovkin, Dmitrii Shestakov, Igor Khatkov, Ekaterina Pismennaya, Vyacheslav Bondarev, Margarita Antyuxina, Elena Shagimardanova, Natalia Bodunova and Oleg Gusev
Int. J. Mol. Sci. 2024, 25(9), 4985; https://doi.org/10.3390/ijms25094985 - 03 May 2024
Abstract
The extraocular muscles (EOMs) possess unique characteristics that set them apart from other skeletal muscles. These muscles, responsible for eye movements, exhibit remarkable resistance to various muscular dystrophies and aging, presenting a significant contrast to the vulnerability of skeletal muscles to these conditions.
[...] Read more.
The extraocular muscles (EOMs) possess unique characteristics that set them apart from other skeletal muscles. These muscles, responsible for eye movements, exhibit remarkable resistance to various muscular dystrophies and aging, presenting a significant contrast to the vulnerability of skeletal muscles to these conditions. In this review, we delve into the cellular and molecular underpinnings of the distinct properties of EOMs. We explore their structural complexity, highlighting differences in fiber types, innervation patterns, and developmental origins. Notably, EOM fibers express a diverse array of myosin heavy-chain isoforms, retaining embryonic forms into adulthood. Moreover, their motor innervation is characterized by a high ratio of nerve fibers to muscle fibers and the presence of unique neuromuscular junctions. These features contribute to the specialized functions of EOMs, including rapid and precise eye movements. Understanding the mechanisms behind the resilience of EOMs to disease and aging may offer insights into potential therapeutic strategies for treating muscular dystrophies and myopathies affecting other skeletal muscles.
Full article
(This article belongs to the Special Issue Skeletal Muscle Function and Metabolism: Molecular Mechanisms and Treatment)
►▼
Show Figures
Figure 1
Open AccessReview
Disuse-Induced Muscle Fatigue: Facts and Assumptions
by
Xenia V. Sergeeva, Irina D. Lvova and Kristina A. Sharlo
Int. J. Mol. Sci. 2024, 25(9), 4984; https://doi.org/10.3390/ijms25094984 - 03 May 2024
Abstract
Skeletal muscle unloading occurs during a wide range of conditions, from space flight to bed rest. The unloaded muscle undergoes negative functional changes, which include increased fatigue. The mechanisms of unloading-induced fatigue are far from complete understanding and cannot be explained by muscle
[...] Read more.
Skeletal muscle unloading occurs during a wide range of conditions, from space flight to bed rest. The unloaded muscle undergoes negative functional changes, which include increased fatigue. The mechanisms of unloading-induced fatigue are far from complete understanding and cannot be explained by muscle atrophy only. In this review, we summarize the data concerning unloading-induced fatigue in different muscles and different unloading models and provide several potential mechanisms of unloading-induced fatigue based on recent experimental data. The unloading-induced changes leading to increased fatigue include both neurobiological and intramuscular processes. The development of intramuscular fatigue seems to be mainly contributed by the transformation of soleus muscle fibers from a fatigue-resistant, “oxidative“ “slow” phenotype to a “fast” “glycolytic“ one. This process includes slow-to-fast fiber-type shift and mitochondrial density decline, as well as the disruption of activating signaling interconnections between slow-type myosin expression and mitochondrial biogenesis. A vast pool of relevant literature suggests that these events are triggered by the inactivation of muscle fibers in the early stages of muscle unloading, leading to the accumulation of high-energy phosphates and calcium ions in the myoplasm, as well as NO decrease. Disturbance of these secondary messengers leads to structural changes in muscles that, in turn, cause increased fatigue.
Full article
(This article belongs to the Special Issue Skeletal Muscle Function and Metabolism: Molecular Mechanisms and Treatment)
►▼
Show Figures
Figure 1
Journal Menu
► ▼ Journal Menu-
- IJMS Home
- Aims & Scope
- Editorial Board
- Reviewer Board
- Topical Advisory Panel
- Instructions for Authors
- Special Issues
- Topics
- Sections & Collections
- Article Processing Charge
- Indexing & Archiving
- Most Cited & Viewed
- Journal Statistics
- Journal History
- Journal Awards
- Society Collaborations
- Conferences
- Editorial Office
Journal Browser
► ▼ Journal Browser-
arrow_forward_ios
Forthcoming issue
arrow_forward_ios Current issue - Vol. 25 (2024)
- Vol. 24 (2023)
- Vol. 23 (2022)
- Vol. 22 (2021)
- Vol. 21 (2020)
- Vol. 20 (2019)
- Vol. 19 (2018)
- Vol. 18 (2017)
- Vol. 17 (2016)
- Vol. 16 (2015)
- Vol. 15 (2014)
- Vol. 14 (2013)
- Vol. 13 (2012)
- Vol. 12 (2011)
- Vol. 11 (2010)
- Vol. 10 (2009)
- Vol. 9 (2008)
- Vol. 8 (2007)
- Vol. 7 (2006)
- Vol. 6 (2005)
- Vol. 5 (2004)
- Vol. 4 (2003)
- Vol. 3 (2002)
- Vol. 2 (2001)
- Vol. 1 (2000)
Highly Accessed Articles
Latest Books
E-Mail Alert
News
Topics
Topic in
Biomedicines, Cells, IJMS, Life, Oxygen
Oxidative Stress and Inflammation, 2nd Volume
Topic Editors: Mohamad Allaw, Ines Castangia, Maria Letizia Manca, Matteo Perra, Amparo NacherDeadline: 31 May 2024
Topic in
BioChem, Biomedicines, Biomolecules, IJMS, Metabolites, Molecules
Natural Products in Prevention and Therapy of Metabolic Syndrome
Topic Editors: Jianbo Wan, Ligen LinDeadline: 30 June 2024
Topic in
Cells, Diseases, Healthcare, IJMS, Vaccines
Inflammation: The Cause of all Diseases 2.0
Topic Editors: Vasso Apostolopoulos, Jack Feehan, Vivek P. ChavdaDeadline: 31 July 2024
Topic in
Biomedicines, CIMB, Endocrines, IJMS, JMP, Life, Reprod. Med.
Pathogenesis of Pregnancy-Related Complications 2.0
Topic Editors: Ilona Hromadnikova, Katerina KotlabovaDeadline: 31 August 2024
Conferences
Special Issues
Special Issue in
IJMS
CRISPR Base Editor for Molecular Plant Sciences
Guest Editor: Weiming HuDeadline: 10 May 2024
Special Issue in
IJMS
Pharmacogenetics and Personalized Medicine 3.0
Guest Editors: José A. Riancho, Gloria RavegniniDeadline: 20 May 2024
Special Issue in
IJMS
Molecular Mechanisms of Angiogenesis and Cancer
Guest Editor: Vijay AvinDeadline: 30 May 2024
Special Issue in
IJMS
Mitochondrial Dysfunction in Neurodegenerative Diseases
Guest Editors: Ashu Johri, Abhishek ChandraDeadline: 10 June 2024
Topical Collections
Topical Collection in
IJMS
Feature Papers in Bioactives and Nutraceuticals
Collection Editor: Maurizio Battino
Topical Collection in
IJMS
State-of-the-Art Molecular Microbiology in Poland
Collection Editors: Alicja Wegrzyn, Satish Raina
Topical Collection in
IJMS
Computational, Structural and Spectroscopic Studies of Enzyme Mechanisms, Inhibition and Dynamics
Collection Editor: Christo Christov