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
Oat Beta-Glucan as a Metabolic Regulator in Early Stage of Colorectal Cancer—A Model Study on Azoxymethane-Treated Rats
Int. J. Mol. Sci. 2024, 25(9), 4635; https://doi.org/10.3390/ijms25094635 (registering DOI) - 24 Apr 2024
Abstract
Factors that reduce the risk of developing colorectal cancer include biologically active substances. In our previous research, we demonstrated the anti-inflammatory, immunomodulatory, and antioxidant effects of oat beta-glucans in gastrointestinal disease models. The aim of this study was to investigate the effect of
[...] Read more.
Factors that reduce the risk of developing colorectal cancer include biologically active substances. In our previous research, we demonstrated the anti-inflammatory, immunomodulatory, and antioxidant effects of oat beta-glucans in gastrointestinal disease models. The aim of this study was to investigate the effect of an 8-week consumption of a diet supplemented with low-molar-mass oat beta-glucan in two doses on the antioxidant potential, inflammatory parameters, and colonic metabolomic profile in azoxymethane(AOM)-induced early-stage colorectal cancer in the large intestine wall of rats. The results showed a statistically significant effect of AOM leading to the development of neoplastic changes in the colon. Consumption of beta-glucans induced changes in colonic antioxidant potential parameters, including an increase in total antioxidant status, a decrease in the superoxide dismutase (SOD) activity, and a reduction in thiobarbituric acid reactive substance (TBARS) concentration. In addition, beta-glucans decreased the levels of pro-inflammatory interleukins (IL-1α, IL-1β, IL-12) and C-reactive protein (CRP) while increasing the concentration of IL-10. Metabolomic studies confirmed the efficacy of oat beta-glucans in the AOM-induced early-stage colon cancer model by increasing the levels of metabolites involved in metabolic pathways, such as amino acids, purine, biotin, and folate. In conclusion, these results suggest a wide range of mechanisms involved in altering colonic metabolism during the early stage of carcinogenesis and a strong influence of low-molar-mass oat beta-glucan, administered as dietary supplement, in modulating these mechanisms.
Full article
(This article belongs to the Special Issue Molecular Mechanisms of Bioactive Nutrients Promoting Human Health)
Open AccessReview
Claudins in Cancer: A Current and Future Therapeutic Target
by
Caroline Hana, Nyein Nyein Thaw Dar, Michael Galo Venegas and Michel Vulfovich
Int. J. Mol. Sci. 2024, 25(9), 4634; https://doi.org/10.3390/ijms25094634 (registering DOI) - 24 Apr 2024
Abstract
Claudins are a family of 27 proteins that have an important role in the formation of tight junctions. They also have an important function in ion exchange, cell mobility, and the epithelial-to-mesenchymal transition, the latter being very important in cancer invasion and metastasis.
[...] Read more.
Claudins are a family of 27 proteins that have an important role in the formation of tight junctions. They also have an important function in ion exchange, cell mobility, and the epithelial-to-mesenchymal transition, the latter being very important in cancer invasion and metastasis. Therapeutic targeting of claudins has been investigated to improve cancer outcomes. Recent evidence shows improved outcomes when combining monoclonal antibodies against claudin 18.2 with chemotherapy for patients with gastroesophageal junction cancer. Currently, chimeric antigen receptor T-cells targeting claudin 18 are under investigation. In this review, we will discuss the major functions of claudins, their distribution in the normal as well as cancerous tissues, and their effect in cancer metastasis, with a special focus on the therapeutic targeting of claudins to improve cancer outcomes.
Full article
(This article belongs to the Special Issue From Basic Science to Treatment Strategies: Personalized Cancer Therapy)
Open AccessReview
RAF and MEK Inhibitors in Non-Small Cell Lung Cancer
by
Christos Adamopoulos, Kostas A. Papavassiliou, Poulikos I. Poulikakos and Athanasios G. Papavassiliou
Int. J. Mol. Sci. 2024, 25(9), 4633; https://doi.org/10.3390/ijms25094633 (registering DOI) - 24 Apr 2024
Abstract
Lung cancer, despite recent advancements in survival rates, represents a significant global health burden. Non-small cell lung cancer (NSCLC), the most prevalent type, is driven largely by activating mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS) and receptor tyrosine kinases (RTKs), and
[...] Read more.
Lung cancer, despite recent advancements in survival rates, represents a significant global health burden. Non-small cell lung cancer (NSCLC), the most prevalent type, is driven largely by activating mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS) and receptor tyrosine kinases (RTKs), and less in v-RAF murine sarcoma viral oncogene homolog B (BRAF) and mitogen-activated protein-kinase kinase (MEK), all key components of the RTK-RAS-mitogen-activated protein kinase (MAPK) pathway. Learning from melanoma, the identification of BRAFV600E substitution in NSCLC provided the rationale for the investigation of RAF and MEK inhibition as a therapeutic strategy. The regulatory approval of two RAF-MEK inhibitor combinations, dabrafenib–trametinib, in 2017, and encorafenib–binimetinib, in 2023, signifies a breakthrough for the management of BRAFV600E-mutant NSCLC patients. However, the almost universal emergence of acquired resistance limits their clinical benefit. New RAF and MEK inhibitors, with distinct biochemical characteristics, are in preclinical and clinical development. In this review, we aim to provide valuable insights into the current state of RAF and MEK inhibition in the management of NSCLC, fostering a deeper understanding of the potential impact on patient outcomes.
Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Open AccessArticle
The Immune Response of OAS1, IRF9, and IFI6 Genes in the Pathogenesis of COVID-19
by
Malena Gajate-Arenas, Ingrid Fricke-Galindo, Omar García-Pérez, Angélica Domínguez-de-Barros, Gloria Pérez-Rubio, Roberto Dorta-Guerra, Ivette Buendía-Roldán, Leslie Chávez-Galán, Jacob Lorenzo-Morales, Ramcés Falfán-Valencia and Elizabeth Córdoba-Lanús
Int. J. Mol. Sci. 2024, 25(9), 4632; https://doi.org/10.3390/ijms25094632 (registering DOI) - 24 Apr 2024
Abstract
COVID-19 is characterized by a wide range of clinical manifestations, where aging, underlying diseases, and genetic background are related to worse outcomes. In the present study, the differential expression of seven genes related to immunity, IRF9, CCL5, IFI6, TGFB1,
[...] Read more.
COVID-19 is characterized by a wide range of clinical manifestations, where aging, underlying diseases, and genetic background are related to worse outcomes. In the present study, the differential expression of seven genes related to immunity, IRF9, CCL5, IFI6, TGFB1, IL1B, OAS1, and TFRC, was analyzed in individuals with COVID-19 diagnoses of different disease severities. Two-step RT-qPCR was performed to determine the relative gene expression in whole-blood samples from 160 individuals. The expression of OAS1 (p < 0.05) and IFI6 (p < 0.05) was higher in moderate hospitalized cases than in severe ones. Increased gene expression of OAS1 (OR = 0.64, CI = 0.52–0.79; p = 0.001), IRF9 (OR = 0.581, CI = 0.43–0.79; p = 0.001), and IFI6 (OR = 0.544, CI = 0.39–0.69; p < 0.001) was associated with a lower risk of requiring IMV. Moreover, TGFB1 (OR = 0.646, CI = 0.50–0.83; p = 0.001), CCL5 (OR = 0.57, CI = 0.39–0.83; p = 0.003), IRF9 (OR = 0.80, CI = 0.653–0.979; p = 0.03), and IFI6 (OR = 0.827, CI = 0.69–0.991; p = 0.039) expression was associated with patient survival. In conclusion, the relevance of OAS1, IRF9, and IFI6 in controlling the viral infection was confirmed.
Full article
(This article belongs to the Special Issue Molecular Research and Insights into COVID-19)
►▼
Show Figures
Figure 1
Open AccessArticle
Podophyllic Aldehyde, a Podophyllotoxin Derivate, Elicits Different Cell Cycle Profiles Depending on the Tumor Cell Line: A Systematic Proteomic Analysis
by
Ángela-Patricia Hernández, Lorea Chaparro-González, Olga Garzo-Sánchez, Carlota Arias-Hidalgo, Pablo Juanes-Velasco, Pablo A. García, Mª Ángeles Castro and Manuel Fuentes
Int. J. Mol. Sci. 2024, 25(9), 4631; https://doi.org/10.3390/ijms25094631 (registering DOI) - 24 Apr 2024
Abstract
When new antitumor therapy drugs are discovered, it is essential to address new target molecules from the point of view of chemical structure and to carry out efficient and systematic evaluation. In the case of natural products and derived compounds, it is of
[...] Read more.
When new antitumor therapy drugs are discovered, it is essential to address new target molecules from the point of view of chemical structure and to carry out efficient and systematic evaluation. In the case of natural products and derived compounds, it is of special importance to investigate chemomodulation to further explore antitumoral pharmacological activities. In this work, the compound podophyllic aldehyde, a cyclolignan derived from the chemomodulation of the natural product podophyllotoxin, has been evaluated for its viability, influence on the cell cycle, and effects on intracellular signaling. We used functional proteomics characterization for the evaluation. Compared with the FDA-approved drug etoposide (another podophyllotoxin derivative), we found interesting results regarding the cytotoxicity of podophyllic aldehyde. In addition, we were able to observe the effect of mitotic arrest in the treated cells. The use of podophyllic aldehyde resulted in increased cytotoxicity in solid tumor cell lines, compared to etoposide, and blocked the cycle more successfully than etoposide. High-throughput analysis of the deregulated proteins revealed a selective antimitotic mechanism of action of podophyllic aldehyde in the HT-29 cell line, in contrast with other solid and hematological tumor lines. Also, the apoptotic profile of podophyllic aldehyde was deciphered. The cell death mechanism is activated independently of the cell cycle profile. The results of these targeted analyses have also shown a significant response to the signaling of kinases, key proteins involved in signaling cascades for cell proliferation or metastasis. Thanks to this comprehensive analysis of podophyllic aldehyde, remarkable cytotoxic, antimitotic, and other antitumoral features have been discovered that will repurpose this compound for further chemical transformations and antitumoral analysis.
Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Pharmacology in Spain 2.0)
►▼
Show Figures
Graphical abstract
Open AccessArticle
A Pilot Immunohistochemical Study Identifies Hedgehog Pathway Expression in Sinonasal Adenocarcinoma
by
Matko Leović, Antonija Jakovčević, Ivan Mumlek, Irena Zagorac, Maja Sabol and Dinko Leović
Int. J. Mol. Sci. 2024, 25(9), 4630; https://doi.org/10.3390/ijms25094630 (registering DOI) - 24 Apr 2024
Abstract
Tumors of the head and neck, more specifically the squamous cell carcinoma, often show upregulation of the Hedgehog signaling pathway. However, almost nothing is known about its role in the sinonasal adenocarcinoma, either in intestinal or non-intestinal subtypes. In this work, we have
[...] Read more.
Tumors of the head and neck, more specifically the squamous cell carcinoma, often show upregulation of the Hedgehog signaling pathway. However, almost nothing is known about its role in the sinonasal adenocarcinoma, either in intestinal or non-intestinal subtypes. In this work, we have analyzed immunohistochemical staining of six Hedgehog pathway proteins, sonic Hedgehog (SHH), Indian Hedgehog (IHH), Patched1 (PTCH1), Gli family zinc finger 1 (GLI1), Gli family zinc finger 2 (GLI2), and Gli family zinc finger 3 (GLI3), on 21 samples of sinonasal adenocarcinoma and compared them with six colon adenocarcinoma and three salivary gland tumors, as well as with matching healthy tissue, where available. We have detected GLI2 and PTCH1 in the majority of samples and also GLI1 in a subset of samples, while GLI3 and the ligands SHH and IHH were generally not detected. PTCH1 pattern of staining shows an interesting pattern, where healthy samples are mostly positive in the stromal compartment, while the signal shifts to the tumor compartment in tumors. This, taken together with a stronger signal of GLI2 in tumors compared to non-tumor tissues, suggests that the Hedgehog pathway is indeed activated in sinonasal adenocarcinoma. As Hedgehog pathway inhibitors are being tested in combination with other therapies for head and neck squamous cell carcinoma, this could provide a therapeutic option for patients with sinonasal adenocarcinoma as well.
Full article
(This article belongs to the Special Issue Pathogenesis and Treatments of Head and Neck Cancer)
►▼
Show Figures
Figure 1
Open AccessReview
Host–Microbiome Crosstalk in Chronic Wound Healing
by
Mara Mădălina Mihai, Beatrice Bălăceanu-Gurău, Ana Ion, Alina Maria Holban, Cristian-Dorin Gurău, Marius Nicolae Popescu, Cristina Beiu, Liliana Gabriela Popa, Mircea Ioan Popa, Cerasella Cristiana Dragomirescu, Mădălina Preda, Alexandru-Andrei Muntean, Ioana Sabina Macovei and Veronica Lazăr
Int. J. Mol. Sci. 2024, 25(9), 4629; https://doi.org/10.3390/ijms25094629 (registering DOI) - 24 Apr 2024
Abstract
The pathogenesis of chronic wounds (CW) involves a multifaceted interplay of biochemical, immunological, hematological, and microbiological interactions. Biofilm development is a significant virulence trait which enhances microbial survival and pathogenicity and has various implications on the development and management of CW. Biofilms induce
[...] Read more.
The pathogenesis of chronic wounds (CW) involves a multifaceted interplay of biochemical, immunological, hematological, and microbiological interactions. Biofilm development is a significant virulence trait which enhances microbial survival and pathogenicity and has various implications on the development and management of CW. Biofilms induce a prolonged suboptimal inflammation in the wound microenvironment, associated with delayed healing. The composition of wound fluid (WF) adds more complexity to the subject, with proven pro-inflammatory properties and an intricate crosstalk among cytokines, chemokines, microRNAs, proteases, growth factors, and ECM components. One approach to achieve information on the mechanisms of disease progression and therapeutic response is the use of multiple high-throughput ‘OMIC’ modalities (genomic, proteomic, lipidomic, metabolomic assays), facilitating the discovery of potential biomarkers for wound healing, which may represent a breakthrough in this field and a major help in addressing delayed wound healing. In this review article, we aim to summarize the current progress achieved in host–microbiome crosstalk in the spectrum of CW healing and highlight future innovative strategies to boost the host immune response against infections, focusing on the interaction between pathogens and their hosts (for instance, by harnessing microorganisms like probiotics), which may serve as the prospective advancement of vaccines and treatments against infections.
Full article
(This article belongs to the Special Issue Microbiome and Skin and Mucocutaneous Diseases)
►▼
Show Figures
Figure 1
Open AccessArticle
Optimization of Pressurized Liquid Extraction (PLE) Parameters for Extraction of Bioactive Compounds from Moringa oleifera Leaves and Bioactivity Assessment
by
Theodoros Chatzimitakos, Vassilis Athanasiadis, Konstantina Kotsou, Martha Mantiniotou, Dimitrios Kalompatsios, Ioannis Makrygiannis, Eleni Bozinou and Stavros I. Lalas
Int. J. Mol. Sci. 2024, 25(9), 4628; https://doi.org/10.3390/ijms25094628 (registering DOI) - 24 Apr 2024
Abstract
Moringa oleifera leaves are rich sources of bioactive compounds with potential health benefits, including antioxidants and anti-inflammatory agents. Pressurized liquid extraction (PLE) stands out as a promising technique for effectively extracting valuable compounds from natural sources. In this study, we aimed to optimize
[...] Read more.
Moringa oleifera leaves are rich sources of bioactive compounds with potential health benefits, including antioxidants and anti-inflammatory agents. Pressurized liquid extraction (PLE) stands out as a promising technique for effectively extracting valuable compounds from natural sources. In this study, we aimed to optimize PLE parameters, such as temperature, extraction duration, and pressure, to maximize bioactive compound (polyphenols, flavonoids, and ascorbic acid) yield from M. oleifera leaves and evaluate their antioxidant and anti-inflammatory activities. According to the outcomes of this research, the maximum achieved total polyphenol content was 24.10 mg gallic acid equivalents (GAE)/g of dry weight (dw), and the total flavonoid content was increased up to 19.89 mg rutin equivalents (RtE)/g dw. Moreover, after HPLC-DAD analysis, neochlorogenic and chlorogenic acids, catechin and epicatechin, rutin, and narirutin were identified and quantified. As far as the optimum ascorbic acid content is concerned, it was found to be 4.77 mg/g dw. The antioxidant activity was evaluated by three different methods: ferric reducing antioxidant power (FRAP), the DPPH method, and the anti-hydrogen peroxide activity (AHPA) method, resulting in 124.29 μmol ascorbic acid equivalent (AAE)/g dw, 131.28 μmol AAE/g dw, and 229.38 μmol AAE/g dw values, respectively. Lastly, the albumin denaturation inhibition was found to be 37.54%. These findings underscore the potential of PLE as an efficient extraction method for preparing extracts from M. oleifera leaves with the maximum content of bioactive compounds.
Full article
(This article belongs to the Special Issue New Applications of Natural Compounds as Functional Additives of Foods)
►▼
Show Figures
Figure 1
Open AccessArticle
An In Vitro Study on the Cytotoxic, Antioxidant, and Antimicrobial Properties of Yamogenin—A Plant Steroidal Saponin and Evaluation of Its Mechanism of Action in Gastric Cancer Cells
by
Justyna Stefanowicz-Hajduk, Piotr Graczyk, Anna Hering, Magdalena Gucwa, Anna Nowak and Rafał Hałasa
Int. J. Mol. Sci. 2024, 25(9), 4627; https://doi.org/10.3390/ijms25094627 (registering DOI) - 24 Apr 2024
Abstract
Yamogenin is a steroidal saponin occurring in plant species such as Asparagus officinalis, Dioscorea collettii, Trigonella foenum-graecum, and Agave sp. In this study, we evaluated in vitro cytotoxic, antioxidant, and antimicrobial properties of yamogenin. The cytotoxic activity was estimated on
[...] Read more.
Yamogenin is a steroidal saponin occurring in plant species such as Asparagus officinalis, Dioscorea collettii, Trigonella foenum-graecum, and Agave sp. In this study, we evaluated in vitro cytotoxic, antioxidant, and antimicrobial properties of yamogenin. The cytotoxic activity was estimated on human colon cancer HCT116, gastric cancer AGS, squamous carcinoma UM-SCC-6 cells, and human normal fibroblasts with MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The amount of apoptotic and dead AGS cells after treatment with yamogenin was estimated with flow cytometry. Also, in yamogenin-treated AGS cells we investigated the reactive oxygen species (ROS) production, mitochondrial membrane depolarization, activity level of caspase-8 and -9, and gene expression at mRNA level with flow cytometry, luminometry, and RT-PCR, respectively. The antioxidant properties of yamogenin were assessed with DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assays. The antimicrobial potential of the compound was estimated on Staphylococcus aureus, Bacillus cereus, Klebsiella pneumoniae, Escherichia coli, Salmonella enterica, Helicobacter pylori, Campylobacter coli, Campylobacter jejuni, Listeria monocytogenes, Lactobacillus paracasei, and Lactobacillus acidophilus bacteria strains. Yamogenin showed the strongest cytotoxic effect on AGS cells (IC50 18.50 ± 1.24 µg/mL) among the tested cell lines. This effect was significantly stronger in combinations of yamogenin with oxaliplatin or capecitabine than for the single compounds. Furthermore, yamogenin induced ROS production, depolarized mitochondrial membrane, and increased the activity level of caspase-8 and -9 in AGS cells. RT-PCR analysis revealed that this sapogenin strongly up-regulated TNFRSF25 expression at the mRNA level. These results indicate that yamogenin induced cell death via the extrinsic and intrinsic way of apoptosis. Antioxidant study showed that yamogenin had moderate in vitro potential (IC50 704.7 ± 5.9 µg/mL in DPPH and 631.09 ± 3.51 µg/mL in ABTS assay) as well as the inhibition of protein denaturation properties (with IC50 1421.92 ± 6.06 µg/mL). Antimicrobial test revealed a weak effect of yamogenin on bacteria strains, the strongest one being against S. aureus (with MIC value of 350 µg/mL). In conclusion, yamogenin may be a potential candidate for the treatment and prevention of gastric cancers.
Full article
(This article belongs to the Special Issue Therapeutic Potential of Natural Compounds: Insights into Mechanisms, Molecular Docking, and Biological Activities)
►▼
Show Figures
Figure 1
Open AccessCommunication
TGFβ-Responsive Stromal Activation Occurs Early in Serrated Colorectal Carcinogenesis
by
Hideaki Tsumuraya, Hirokazu Okayama, Masanori Katagata, Akira Matsuishi, Satoshi Fukai, Misato Ito, Wataru Sakamoto, Motonobu Saito, Tomoyuki Momma, Shotaro Nakajima, Kosaku Mimura and Koji Kono
Int. J. Mol. Sci. 2024, 25(9), 4626; https://doi.org/10.3390/ijms25094626 (registering DOI) - 24 Apr 2024
Abstract
Activated TGFβ signaling in the tumor microenvironment, which occurs independently of epithelial cancer cells, has emerged as a key driver of tumor progression in late-stage colorectal cancer (CRC). This study aimed to elucidate the contribution of TGFβ-activated stroma to serrated carcinogenesis, representing approximately
[...] Read more.
Activated TGFβ signaling in the tumor microenvironment, which occurs independently of epithelial cancer cells, has emerged as a key driver of tumor progression in late-stage colorectal cancer (CRC). This study aimed to elucidate the contribution of TGFβ-activated stroma to serrated carcinogenesis, representing approximately 25% of CRCs and often characterized by oncogenic BRAF mutations. We used a transcriptional signature developed based on TGFβ-responsive, stroma-specific genes to infer TGFβ-dependent stromal activation and conducted in silico analyses in 3 single-cell RNA-seq datasets from a total of 39 CRC samples and 12 bulk transcriptomic datasets consisting of 2014 CRC and 416 precursor samples, of which 33 were serrated lesions. Single-cell analyses validated that the signature was expressed specifically by stromal cells, effectively excluding transcriptional signals derived from epithelial cells. We found that the signature was upregulated during malignant transformation and cancer progression, and it was particularly enriched in CRCs with mutant BRAF compared to wild-type counterparts. Furthermore, across four independent precursor datasets, serrated lesions exhibited significantly higher levels of TGFβ-responsive stromal activation compared to conventional adenomas. This large-scale analysis suggests that TGFβ-dependent stromal activation occurs early in serrated carcinogenesis. Our study provides novel insights into the molecular mechanisms underlying CRC development via the serrated pathway.
Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapies of Colorectal Cancer 3.0)
►▼
Show Figures
Figure 1
Open AccessArticle
Glycosylation and Characterization of Human Transferrin in an End-Stage Kidney Disease
by
Goran Miljuš, Ana Penezić, Lucia Pažitná, Nikola Gligorijević, Marko Baralić, Aleksandra Vilotić, Miloš Šunderić, Dragana Robajac, Zorana Dobrijević, Jaroslav Katrlík and Olgica Nedić
Int. J. Mol. Sci. 2024, 25(9), 4625; https://doi.org/10.3390/ijms25094625 - 24 Apr 2024
Abstract
Chronic kidney disease (CKD) is a global health concern affecting approximately one billion individuals worldwide. End-stage kidney disease (ESKD), the most severe form of CKD, is often accompanied by anemia. Peritoneal dialysis (PD), a common treatment for ESKD, utilizes the peritoneum for solute
[...] Read more.
Chronic kidney disease (CKD) is a global health concern affecting approximately one billion individuals worldwide. End-stage kidney disease (ESKD), the most severe form of CKD, is often accompanied by anemia. Peritoneal dialysis (PD), a common treatment for ESKD, utilizes the peritoneum for solute transfer but is associated with complications including protein loss, including transferrin (Tf) a key protein involved in iron transport. This study investigated Tf characteristics in ESKD patients compared to healthy individuals using lectin microarray, spectroscopic techniques and immunocytochemical analysis to assess Tf interaction with transferrin receptors (TfRs). ESKD patients exhibited altered Tf glycosylation patterns, evidenced by significant changes in lectin reactivity compared to healthy controls. However, structural analyses revealed no significant differences in the Tf secondary or tertiary structures between the two groups. A functional analysis demonstrated comparable Tf-TfR interaction in both PD and healthy samples. Despite significant alterations in Tf glycosylation, structural integrity and Tf-TfR interaction remained preserved in PD patients. These findings suggest that while glycosylation changes may influence iron metabolism, they do not impair Tf function. The study highlights the importance of a glucose-free dialysis solutions in managing anemia exacerbation in PD patients with poorly controlled anemia, potentially offering a targeted therapeutic approach to improve patient outcomes.
Full article
(This article belongs to the Special Issue Glycobiology: The New Discoveries, Approaches, and Technical Developments)
►▼
Show Figures
Figure 1
Open AccessReview
Homologous Recombination Repair Deficiency in Metastatic Prostate Cancer: New Therapeutic Opportunities
by
Claudia Piombino, Stefania Pipitone, Elena Tonni, Luciana Mastrodomenico, Marco Oltrecolli, Cyrielle Tchawa, Rossana Matranga, Sara Roccabruna, Elisa D’Agostino, Marta Pirola, Francesca Bacchelli, Cinzia Baldessari, Maria Cristina Baschieri, Massimo Dominici, Roberto Sabbatini and Maria Giuseppa Vitale
Int. J. Mol. Sci. 2024, 25(9), 4624; https://doi.org/10.3390/ijms25094624 (registering DOI) - 24 Apr 2024
Abstract
More than 20% of metastatic prostate cancer carries genomic defects involving DNA damage repair pathways, mainly in homologous recombination repair-related genes. The recent approval of olaparib has paved the way to precision medicine for the treatment of metastatic prostate cancer with PARP inhibitors
[...] Read more.
More than 20% of metastatic prostate cancer carries genomic defects involving DNA damage repair pathways, mainly in homologous recombination repair-related genes. The recent approval of olaparib has paved the way to precision medicine for the treatment of metastatic prostate cancer with PARP inhibitors in this subset of patients, especially in the case of BRCA1 or BRCA2 pathogenic/likely pathogenic variants. In face of this new therapeutic opportunity, many issues remain unsolved. This narrative review aims to describe the relationship between homologous recombination repair deficiency and prostate cancer, the techniques used to determine homologous recombination repair status in prostate cancer, the crosstalk between homologous recombination repair and the androgen receptor pathway, the current evidence on PARP inhibitors activity in metastatic prostate cancer also in homologous recombination repair-proficient tumors, as well as emerging mechanisms of resistance to PARP inhibitors. The possibility of combination therapies including a PARP inhibitor is an attractive option, and more robust data are awaited from ongoing phase II and phase III trials outlined in this manuscript.
Full article
(This article belongs to the Special Issue Molecular Research on Prostate Cancer)
►▼
Show Figures
Figure 1
Open AccessArticle
Verification of AKT and CDK5 Gene and RNA Interference Combined with Irradiation to Mediate Fertility Changes in Plutella xylostella (Linnaeus)
by
Jiaqi Wen, Mengran Wang, Yuhao Zeng, Fengting He, Shifan Li, Ke Zhang and Qunfang Weng
Int. J. Mol. Sci. 2024, 25(9), 4623; https://doi.org/10.3390/ijms25094623 - 24 Apr 2024
Abstract
Plutella xylostella (Linnaeus) mainly damages cruciferous crops and causes huge economic losses. Presently, chemical pesticides dominate its control, but prolonged use has led to the development of high resistance. In contrast, the sterile insect technique provides a preventive and control method to avoid
[...] Read more.
Plutella xylostella (Linnaeus) mainly damages cruciferous crops and causes huge economic losses. Presently, chemical pesticides dominate its control, but prolonged use has led to the development of high resistance. In contrast, the sterile insect technique provides a preventive and control method to avoid the development of resistance. We discovered two genes related to the reproduction of Plutella xylostella and investigated the efficacy of combining irradiation with RNA interference for pest management. The results demonstrate that after injecting PxAKT and PxCDK5, there was a significant decrease of 28.06% and 25.64% in egg production, and a decrease of 19.09% and 15.35% in the hatching rate compared to the control. The ratio of eupyrene sperm bundles to apyrene sperm bundles also decreased. PxAKT and PxCDK5 were identified as pivotal genes influencing male reproductive processes. We established a dose-response relationship for irradiation (0–200 Gy and 200–400 Gy) and derived the irradiation dose equivalent to RNA interference targeting PxAKT and PxCDK5. Combining RNA interference with low-dose irradiation achieved a sub-sterile effect on Plutella xylostella, surpassing either irradiation or RNA interference alone. This study enhances our understanding of the genes associated with the reproduction of Plutella xylostella and proposes a novel approach for pest management by combining irradiation and RNA interference.
Full article
(This article belongs to the Section Molecular Genetics and Genomics)
►▼
Show Figures
Figure 1
Open AccessArticle
Computational Design of Novel Cyclic Peptides Endowed with Autophagy-Inhibiting Activity on Cancer Cell Lines
by
Marco Albani, Enrico Mario Alessandro Fassi, Roberta Manuela Moretti, Mariangela Garofalo, Marina Montagnani Marelli, Gabriella Roda, Jacopo Sgrignani, Andrea Cavalli and Giovanni Grazioso
Int. J. Mol. Sci. 2024, 25(9), 4622; https://doi.org/10.3390/ijms25094622 - 24 Apr 2024
Abstract
(1) Autophagy plays a significant role in development and cell proliferation. This process is mainly accomplished by the LC3 protein, which, after maturation, builds the nascent autophagosomes. The inhibition of LC3 maturation results in the interference of autophagy activation. (2) In this study,
[...] Read more.
(1) Autophagy plays a significant role in development and cell proliferation. This process is mainly accomplished by the LC3 protein, which, after maturation, builds the nascent autophagosomes. The inhibition of LC3 maturation results in the interference of autophagy activation. (2) In this study, starting from the structure of a known LC3B binder (LIR2-RavZ peptide), we identified new LC3B ligands by applying an in silico drug design strategy. The most promising peptides were synthesized, biophysically assayed, and biologically evaluated to ascertain their potential antiproliferative activity on five humans cell lines. (3) A cyclic peptide (named Pep6), endowed with high conformational stability (due to the presence of a disulfide bridge), displayed a Kd value on LC3B in the nanomolar range. Assays accomplished on PC3, MCF-7, and A549 cancer cell lines proved that Pep6 exhibited cytotoxic effects comparable to those of the peptide LIR2-RavZ, a reference LC3B ligand. Furthermore, it was ineffective on both normal prostatic epithelium PNT2 and autophagy-defective prostate cancer DU145 cells. (4) Pep6 can be considered a new autophagy inhibitor that can be employed as a pharmacological tool or even as a template for the rational design of new small molecules endowed with autophagy inhibitory activity.
Full article
(This article belongs to the Special Issue Drug Discovery: Design, Synthesis and Activity Evaluation)
►▼
Show Figures
Graphical abstract
Open AccessArticle
Reduced Expression of CLEC4G in Neurons Is Associated with Alzheimer’s Disease
by
Xinwei Feng, Fangfang Qi, Yuying Huang, Ge Zhang and Wenbin Deng
Int. J. Mol. Sci. 2024, 25(9), 4621; https://doi.org/10.3390/ijms25094621 - 24 Apr 2024
Abstract
CLEC4G, a glycan-binding receptor, has previously been demonstrated to inhibit Aβ generation, yet its brain localization and functions in Alzheimer’s disease (AD) are not clear. We explored the localization, function, and regulatory network of CLEC4G via experiments and analysis of RNA-seq databases. CLEC4G
[...] Read more.
CLEC4G, a glycan-binding receptor, has previously been demonstrated to inhibit Aβ generation, yet its brain localization and functions in Alzheimer’s disease (AD) are not clear. We explored the localization, function, and regulatory network of CLEC4G via experiments and analysis of RNA-seq databases. CLEC4G transcripts and proteins were identified in brain tissues, with the highest expression observed in neurons. Notably, AD was associated with reduced levels of CLEC4G transcripts. Bioinformatic analyses revealed interactions between CLEC4G and relevant genes such as BACE1, NPC1, PILRA, TYROBP, MGAT1, and MGAT3, all displaying a negative correlation trend. We further identified the upstream transcriptional regulators NR2F6 and XRCC4 for CLEC4G and confirmed a decrease in CLEC4G expression in APP/PS1 transgenic mice. This study highlights the role of CLEC4G in protecting against AD progression and the significance of CLEC4G for AD research and management.
Full article
(This article belongs to the Special Issue Advances in Aging and Alzheimer’s Disease Research: From Molecular Mechanisms to Therapeutics)
►▼
Show Figures
Figure 1
Open AccessReview
Biological Roles and Clinical Applications of Exosomes in Breast Cancer: A Brief Review
by
Han Wang, Ruo Wang, Kunwei Shen, Renhong Huang and Zheng Wang
Int. J. Mol. Sci. 2024, 25(9), 4620; https://doi.org/10.3390/ijms25094620 - 24 Apr 2024
Abstract
Breast cancer (BC) is a global health risk for women and has a high prevalence rate. The drug resistance, recurrence, and metastasis of BC affect patient prognosis, thus posing a challenge to scientists. Exosomes are extracellular vesicles (EVs) that originate from various cells;
[...] Read more.
Breast cancer (BC) is a global health risk for women and has a high prevalence rate. The drug resistance, recurrence, and metastasis of BC affect patient prognosis, thus posing a challenge to scientists. Exosomes are extracellular vesicles (EVs) that originate from various cells; they have a double-layered lipid membrane structure and contain rich biological information. They mediate intercellular communication and have pivotal roles in tumor development, progression, and metastasis and drug resistance. Exosomes are important cell communication mediators in the tumor microenvironment (TME). Exosomes are utilized as diagnostic and prognostic biomarkers for estimating the treatment efficacy of BC and have the potential to function as tools to enable the targeted delivery of antitumor drugs. This review introduces recent progress in research on how exosomes influence tumor development and the TME. We also present the research progress on the application of exosomes as prognostic and diagnostic biomarkers and drug delivery tools.
Full article
(This article belongs to the Special Issue Molecular Research and Treatment of Breast Cancer 3.0)
►▼
Show Figures
Figure 1
Open AccessArticle
Synergistic Effect of Dietary Supplementation with Sodium Butyrate, β-Glucan and Vitamins on Growth Performance, Cortisol Level, Intestinal Microbiome and Expression of Immune-Related Genes in Juvenile African Catfish (Clarias gariepinus)
by
Martyna Arciuch-Rutkowska, Joanna Nowosad, Łukasz Gil, Urszula Czarnik and Dariusz Kucharczyk
Int. J. Mol. Sci. 2024, 25(9), 4619; https://doi.org/10.3390/ijms25094619 - 24 Apr 2024
Abstract
The effect of dietary supplementation with sodium butyrate, β-glucan and vitamins (A, D3, E, K, C) on breeding indicators and immune parameters of juvenile African catfish was examined. The fish were fed with unenriched (group C) and enriched feed with a variable proportion
[...] Read more.
The effect of dietary supplementation with sodium butyrate, β-glucan and vitamins (A, D3, E, K, C) on breeding indicators and immune parameters of juvenile African catfish was examined. The fish were fed with unenriched (group C) and enriched feed with a variable proportion of sodium butyrate/β-glucan, and constant content of vitamins (W1–W3). After the experiment, blood and the middle gut were collected. The microbiome of the gut was determined using Next Generation Sequencing (NGS). Liver tissue was collected for determination of expression of immune-related genes (HSP70, IL-1β, TNFα). W2 and W3 were characterized by the most favorable values of breeding indicators (p < 0.05). The highest blood cortisol concentration was in group C (71.25 ± 10.45 ng/mL), and significantly the lowest in W1 (46.03 ± 7.01 ng/ mL) (p < 0.05). The dominance of Cetobacterium was observed in all study groups, with the largest share in W3 (65.25%) and W1 (61.44%). Gene expression showed an increased number of HSP70 genes in W1. IL-1β and TNFα genes peaked at W3. The W3 variant turns out to be the most beneficial supplementation, due to the improvement of breeding and immunological parameters. The data obtained can be used to create a preparation for commercial use in the breeding of this species.
Full article
(This article belongs to the Special Issue 25 Anniversary of Bioinformatics of Genome Regulation and Structure Conference Series)
►▼
Show Figures
Figure 1
Open AccessArticle
Systems Biology for Drug Target Discovery in Acute Myeloid Leukemia
by
Svetlana Novikova, Tatiana Tolstova, Leonid Kurbatov, Tatiana Farafonova, Olga Tikhonova, Natalia Soloveva, Alexander Rusanov and Victor Zgoda
Int. J. Mol. Sci. 2024, 25(9), 4618; https://doi.org/10.3390/ijms25094618 - 23 Apr 2024
Abstract
Combining new therapeutics with all-trans-retinoic acid (ATRA) could improve the efficiency of acute myeloid leukemia (AML) treatment. Modeling the process of ATRA-induced differentiation based on the transcriptomic profile of leukemic cells resulted in the identification of key targets that can be
[...] Read more.
Combining new therapeutics with all-trans-retinoic acid (ATRA) could improve the efficiency of acute myeloid leukemia (AML) treatment. Modeling the process of ATRA-induced differentiation based on the transcriptomic profile of leukemic cells resulted in the identification of key targets that can be used to increase the therapeutic effect of ATRA. The genome-scale transcriptome analysis revealed the early molecular response to the ATRA treatment of HL-60 cells. In this study, we performed the transcriptomic profiling of HL-60, NB4, and K562 cells exposed to ATRA for 3-72 h. After treatment with ATRA for 3, 12, 24, and 72 h, we found 222, 391, 359, and 1032 differentially expressed genes (DEGs) in HL-60 cells, as well as 641, 1037, 1011, and 1499 DEGs in NB4 cells. We also found 538 and 119 DEGs in K562 cells treated with ATRA for 24 h and 72 h, respectively. Based on experimental transcriptomic data, we performed hierarchical modeling and determined cyclin-dependent kinase 6 (CDK6), tumor necrosis factor alpha (TNF-alpha), and transcriptional repressor CUX1 as the key regulators of the molecular response to the ATRA treatment in HL-60, NB4, and K562 cell lines, respectively. Mapping the data of TMT-based mass-spectrometric profiling on the modeling schemes, we determined CDK6 expression at the proteome level and its down-regulation at the transcriptome and proteome levels in cells treated with ATRA for 72 h. The combination of therapy with a CDK6 inhibitor (palbociclib) and ATRA (tretinoin) could be an alternative approach for the treatment of acute myeloid leukemia (AML).
Full article
(This article belongs to the Collection Feature Paper Collection in Biochemistry)
Open AccessArticle
Development of a New Model System to Study Long-Distance Interactions Supported by Architectural Proteins
by
Larisa Melnikova, Varvara Molodina, Pavel Georgiev and Anton Golovnin
Int. J. Mol. Sci. 2024, 25(9), 4617; https://doi.org/10.3390/ijms25094617 - 23 Apr 2024
Abstract
Chromatin architecture is critical for the temporal and tissue-specific activation of genes that determine eukaryotic development. The functional interaction between enhancers and promoters is controlled by insulators and tethering elements that support specific long-distance interactions. However, the mechanisms of the formation and maintenance
[...] Read more.
Chromatin architecture is critical for the temporal and tissue-specific activation of genes that determine eukaryotic development. The functional interaction between enhancers and promoters is controlled by insulators and tethering elements that support specific long-distance interactions. However, the mechanisms of the formation and maintenance of long-range interactions between genome regulatory elements remain poorly understood, primarily due to the lack of convenient model systems. Drosophila became the first model organism in which architectural proteins that determine the activity of insulators were described. In Drosophila, one of the best-studied DNA-binding architectural proteins, Su(Hw), forms a complex with Mod(mdg4)-67.2 and CP190 proteins. Using a combination of CRISPR/Cas9 genome editing and attP-dependent integration technologies, we created a model system in which the promoters and enhancers of two reporter genes are separated by 28 kb. In this case, enhancers effectively stimulate reporter gene promoters in cis and trans only in the presence of artificial Su(Hw) binding sites (SBS), in both constructs. The expression of the mutant Su(Hw) protein, which cannot interact with CP190, and the mutation inactivating Mod(mdg4)-67.2, lead to the complete loss or significant weakening of enhancer–promoter interactions, respectively. The results indicate that the new model system effectively identifies the role of individual subunits of architectural protein complexes in forming and maintaining specific long-distance interactions in the D. melanogaster model.
Full article
(This article belongs to the Special Issue Molecular Genetics of Drosophila Development)
Open AccessArticle
TRIM44 Promotes Rabies Virus Replication by Autophagy-Dependent Mechanism
by
Hongling He, Ting Cai, Qiaozhu Chen, Zilian Chen, Boyue Zhang, Changyi Chen, Yueze Wang, Yan Liu, Yueming Wang, Yongwen Luo, Shile Huang, Jun Luo and Xiaofeng Guo
Int. J. Mol. Sci. 2024, 25(9), 4616; https://doi.org/10.3390/ijms25094616 - 23 Apr 2024
Abstract
Tripartite motif (TRIM) proteins are a multifunctional E3 ubiquitin ligase family that participates in various cellular processes. Recent studies have shown that TRIM proteins play important roles in regulating host–virus interactions through specific pathways, but their involvement in response to rabies virus (RABV)
[...] Read more.
Tripartite motif (TRIM) proteins are a multifunctional E3 ubiquitin ligase family that participates in various cellular processes. Recent studies have shown that TRIM proteins play important roles in regulating host–virus interactions through specific pathways, but their involvement in response to rabies virus (RABV) infection remains poorly understood. Here, we identified that several TRIM proteins are upregulated in mouse neuroblastoma cells (NA) after infection with the rabies virus using RNA-seq sequencing. Among them, TRIM44 was found to regulate RABV replication. This is supported by the observations that downregulation of TRIM44 inhibits RABV replication, while overexpression of TRIM44 promotes RABV replication. Mechanistically, TRIM44-induced RABV replication is brought about by activating autophagy, as inhibition of autophagy with 3-MA attenuates TRIM44-induced RABV replication. Additionally, we found that inhibition of autophagy with rapamycin reverses the TRIM44-knockdown-induced decrease in LC3B expression and autophagosome formation as well as RABV replication. The results suggest that TRIM44 promotes RABV replication by an autophagy-dependent mechanism. Our work identifies TRIM44 as a key host factor for RABV replication, and targeting TRIM44 expression may represent an effective therapeutic strategy.
Full article
(This article belongs to the Section Molecular Microbiology)
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
Structural Dynamics of Macromolecules
Guest Editor: Ki Hyun NamDeadline: 25 April 2024
Special Issue in
IJMS
Monoclonal Antibodies and Their Functional Fragments in Research, Diagnosis and Therapy 3.0
Guest Editors: Menotti Ruvo, Annamaria SandomenicoDeadline: 30 April 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
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