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
Deciphering the Impact of Defecation Frequency on Gut Microbiome Composition and Diversity
Int. J. Mol. Sci. 2024, 25(9), 4657; https://doi.org/10.3390/ijms25094657 (registering DOI) - 25 Apr 2024
Abstract
This study explores the impact of defecation frequency on the gut microbiome structure by analyzing fecal samples from individuals categorized by defecation frequency: infrequent (1–3 times/week, n = 4), mid-frequent (4–6 times/week, n = 7), and frequent (daily, n = 9). Utilizing 16S
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This study explores the impact of defecation frequency on the gut microbiome structure by analyzing fecal samples from individuals categorized by defecation frequency: infrequent (1–3 times/week, n = 4), mid-frequent (4–6 times/week, n = 7), and frequent (daily, n = 9). Utilizing 16S rRNA gene-based sequencing and LC-MS/MS metabolome profiling, significant differences in microbial diversity and community structures among the groups were observed. The infrequent group showed higher microbial diversity, with community structures significantly varying with defecation frequency, a pattern consistent across all sampling time points. The Ruminococcus genus was predominant in the infrequent group, but decreased with more frequent defecation, while the Bacteroides genus was more common in the frequent group, decreasing as defecation frequency lessened. The infrequent group demonstrated enriched biosynthesis genes for aromatic amino acids and branched-chain amino acids (BCAAs), in contrast to the frequent group, which had a higher prevalence of genes for BCAA catabolism. Metabolome analysis revealed higher levels of metabolites derived from aromatic amino acids and BCAA metabolism in the infrequent group, and lower levels of BCAA-derived metabolites in the frequent group, consistent with their predicted metagenomic functions. These findings underscore the importance of considering stool consistency/frequency in understanding the factors influencing the gut microbiome.
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(This article belongs to the Special Issue New Molecular Insights into the Gut Microbiome)
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A Mass Spectrometry Strategy for Protein Quantification Based on the Differential Alkylation of Cysteines Using Iodoacetamide and Acrylamide
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Dávid Virág, Gitta Schlosser, Adina Borbély, Gabriella Gellén, Dávid Papp, Zoltán Kaleta, Borbála Dalmadi-Kiss, István Antal and Krisztina Ludányi
Int. J. Mol. Sci. 2024, 25(9), 4656; https://doi.org/10.3390/ijms25094656 (registering DOI) - 25 Apr 2024
Abstract
Mass spectrometry has become the most prominent yet evolving technology in quantitative proteomics. Today, a number of label-free and label-based approaches are available for the relative and absolute quantification of proteins and peptides. However, the label-based methods rely solely on the employment of
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Mass spectrometry has become the most prominent yet evolving technology in quantitative proteomics. Today, a number of label-free and label-based approaches are available for the relative and absolute quantification of proteins and peptides. However, the label-based methods rely solely on the employment of stable isotopes, which are expensive and often limited in availability. Here we propose a label-based quantification strategy, where the mass difference is identified by the differential alkylation of cysteines using iodoacetamide and acrylamide. The alkylation reactions were performed under identical experimental conditions; therefore, the method can be easily integrated into standard proteomic workflows. Using high-resolution mass spectrometry, the feasibility of this approach was assessed with a set of tryptic peptides of human serum albumin. Several critical questions, such as the efficiency of labeling and the effect of the differential alkylation on the peptide retention and fragmentation, were addressed. The concentration of the quality control samples calculated against the calibration curves were within the ±20% acceptance range. It was also demonstrated that heavy labeled peptides exhibit a similar extraction recovery and matrix effect to light ones. Consequently, the approach presented here may be a viable and cost-effective alternative of stable isotope labeling strategies for the quantification of cysteine-containing proteins.
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(This article belongs to the Special Issue High Resolution Mass Spectrometry in Molecular Sciences: 2nd Edition)
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Open AccessArticle
Peptides Targeting the IF1–ATP Synthase Complex Modulate the Permeability Transition Pore in Cancer HeLa Cells
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Martina Grandi, Simone Fabbian, Giancarlo Solaini, Alessandra Baracca, Massimo Bellanda and Valentina Giorgio
Int. J. Mol. Sci. 2024, 25(9), 4655; https://doi.org/10.3390/ijms25094655 (registering DOI) - 25 Apr 2024
Abstract
The mitochondrial protein IF1 is upregulated in many tumors and acts as a pro-oncogenic protein through its interaction with the ATP synthase and the inhibition of apoptosis. We have recently characterized the molecular nature of the IF1–Oligomycin Sensitivity Conferring Protein (OSCP) subunit interaction;
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The mitochondrial protein IF1 is upregulated in many tumors and acts as a pro-oncogenic protein through its interaction with the ATP synthase and the inhibition of apoptosis. We have recently characterized the molecular nature of the IF1–Oligomycin Sensitivity Conferring Protein (OSCP) subunit interaction; however, it remains to be determined whether this interaction could be targeted for novel anti-cancer therapeutic intervention. We generated mitochondria-targeting peptides to displace IF1 from the OSCP interaction. The use of one selective peptide led to displacement of the inhibitor IF1 from ATP synthase, as shown by immunoprecipitation. NMR spectroscopy analysis, aimed at clarifying whether these peptides were able to directly bind to the OSCP protein, identified a second peptide which showed affinity for the N-terminal region of this subunit overlapping the IF1 binding region. In situ treatment with the membrane-permeable derivatives of these peptides in HeLa cells, that are silenced for the IF1 inhibitor protein, showed significant inhibition in mitochondrial permeability transition and no effects on mitochondrial respiration. These peptides mimic the effects of the IF1 inhibitor protein in cancer HeLa cells and confirm that the IF1–OSCP interaction inhibits apoptosis. A third peptide was identified which counteracts the anti-apoptotic role of IF1, showing that OSCP is a promising target for anti-cancer therapies.
Full article
(This article belongs to the Section Molecular Oncology)
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Open AccessReview
The Importance and Essentiality of Natural and Synthetic Chelators in Medicine: Increased Prospects for the Effective Treatment of Iron Overload and Iron Deficiency
by
George J. Kontoghiorghes
Int. J. Mol. Sci. 2024, 25(9), 4654; https://doi.org/10.3390/ijms25094654 (registering DOI) - 25 Apr 2024
Abstract
The supply and control of iron is essential for all cells and vital for many physiological processes. All functions and activities of iron are expressed in conjunction with iron-binding molecules. For example, natural chelators such as transferrin and chelator–iron complexes such as haem
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The supply and control of iron is essential for all cells and vital for many physiological processes. All functions and activities of iron are expressed in conjunction with iron-binding molecules. For example, natural chelators such as transferrin and chelator–iron complexes such as haem play major roles in iron metabolism and human physiology. Similarly, the mainstay treatments of the most common diseases of iron metabolism, namely iron deficiency anaemia and iron overload, involve many iron–chelator complexes and the iron-chelating drugs deferiprone (L1), deferoxamine (DF) and deferasirox. Endogenous chelators such as citric acid and glutathione and exogenous chelators such as ascorbic acid also play important roles in iron metabolism and iron homeostasis. Recent advances in the treatment of iron deficiency anaemia with effective iron complexes such as the ferric iron tri-maltol complex (feraccru or accrufer) and the effective treatment of transfusional iron overload using L1 and L1/DF combinations have decreased associated mortality and morbidity and also improved the quality of life of millions of patients. Many other chelating drugs such as ciclopirox, dexrazoxane and EDTA are used daily by millions of patients in other diseases. Similarly, many other drugs or their metabolites with iron-chelation capacity such as hydroxyurea, tetracyclines, anthracyclines and aspirin, as well as dietary molecules such as gallic acid, caffeic acid, quercetin, ellagic acid, maltol and many other phytochelators, are known to interact with iron and affect iron metabolism and related diseases. Different interactions are also observed in the presence of essential, xenobiotic, diagnostic and theranostic metal ions competing with iron. Clinical trials using L1 in Parkinson’s, Alzheimer’s and other neurodegenerative diseases, as well as HIV and other infections, cancer, diabetic nephropathy and anaemia of inflammation, highlight the importance of chelation therapy in many other clinical conditions. The proposed use of iron chelators for modulating ferroptosis signifies a new era in the design of new therapeutic chelation strategies in many other diseases. The introduction of artificial intelligence guidance for optimal chelation therapeutic outcomes in personalised medicine is expected to increase further the impact of chelation in medicine, as well as the survival and quality of life of millions of patients with iron metabolic disorders and also other diseases.
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(This article belongs to the Section Molecular Pharmacology)
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An Update on Implant-Associated Malignancies and Their Biocompatibility
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Grace C. Keane Tahmaseb, Alexandra M. Keane, Jose A. Foppiani and Terence M. Myckatyn
Int. J. Mol. Sci. 2024, 25(9), 4653; https://doi.org/10.3390/ijms25094653 (registering DOI) - 24 Apr 2024
Abstract
Implanted medical devices are widely used across various medical specialties for numerous applications, ranging from cardiovascular supports to orthopedic prostheses and cosmetic enhancements. However, recent observations have raised concerns about the potential of these implants to induce malignancies in the tissues surrounding them.
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Implanted medical devices are widely used across various medical specialties for numerous applications, ranging from cardiovascular supports to orthopedic prostheses and cosmetic enhancements. However, recent observations have raised concerns about the potential of these implants to induce malignancies in the tissues surrounding them. There have been several case reports documenting the occurrence of cancers adjacent to these devices, prompting a closer examination of their safety. This review delves into the epidemiology, clinical presentations, pathological findings, and hypothesized mechanisms of carcinogenesis related to implanted devices. It also explores how the surgical domain and the intrinsic properties and biocompatibility of the implants might influence the development of these rare but serious malignancies. Understanding these associations is crucial for assessing the risks associated with the use of medical implants, and for developing strategies to mitigate potential adverse outcomes.
Full article
(This article belongs to the Special Issue Beyond Compatibility: Unraveling the Molecular Dynamics of Biomaterial-Host Interactions)
Open AccessArticle
Testosterone Enhances KV Currents and Airway Smooth Muscle Relaxation Induced by ATP and UTP through P2Y4 Receptors and Adenylyl Cyclase Pathway
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Abril Carbajal-García, Jorge Reyes-García, Verónica Díaz-Hernández, María F. Casas-Hernández, Francisco Javier Flores-Murrieta and Luis M. Montaño
Int. J. Mol. Sci. 2024, 25(9), 4652; https://doi.org/10.3390/ijms25094652 (registering DOI) - 24 Apr 2024
Abstract
Numerous studies suggest the involvement of adenosine-5′-triphosphate (ATP) and similar nucleotides in the pathophysiology of asthma. Androgens, such as testosterone (TES), are proposed to alleviate asthma symptoms in young men. ATP and uridine-5′-triphosphate (UTP) relax the airway smooth muscle (ASM) via purinergic P2Y
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Numerous studies suggest the involvement of adenosine-5′-triphosphate (ATP) and similar nucleotides in the pathophysiology of asthma. Androgens, such as testosterone (TES), are proposed to alleviate asthma symptoms in young men. ATP and uridine-5′-triphosphate (UTP) relax the airway smooth muscle (ASM) via purinergic P2Y2 and P2Y4 receptors and K+ channel opening. We previously demonstrated that TES increased the expression of voltage-dependent K+ (KV) channels in ASM. This study investigates how TES may potentiate ASM relaxation induced by ATP and UTP. Tracheal tissues treated with or without TES (control group) from young male guinea pigs were used. In organ baths, tracheas exposed to TES (40 nM for 48 h) showed enhanced ATP- and UTP-evoked relaxation. Tetraethylammonium, a K+ channel blocker, annulled this effect. Patch-clamp experiments in tracheal myocytes showed that TES also increased ATP- and UTP-induced K+ currents, and this effect was abolished with flutamide (an androgen receptor antagonist). KV channels were involved in this phenomenon, which was demonstrated by inhibition with 4-aminopyridine. RB2 (an antagonist of almost all P2Y receptors except for P2Y2), as well as N-ethylmaleimide and SQ 22,536 (inhibitors of G proteins and adenylyl cyclase, respectively), attenuated the enhancement of the K+ currents induced by TES. Immunofluorescence and immunohistochemistry studies revealed that TES did not modify the expression of P2Y4 receptors or COX-1 and COX-2, while we have demonstrated that this androgen augmented the expression of KV1.2 and KV1.5 channels in ASM. Thus, TES leads to the upregulation of P2Y4 signaling and KV channels in guinea pig ASM, enhancing ATP and UTP relaxation responses, which likely limits the severity of bronchospasm in young males.
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(This article belongs to the Special Issue Ion Movements and Membrane Proteins)
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Transcranial Magneto-Acoustic Stimulation Protects Synaptic Rehabilitation from Amyloid-Beta Plaques via Regulation of Microglial Functions
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Chunlan Zhang, Ruxin Tan, Xiaoqing Zhou, Ruru Wang, Xin Wang, Ren Ma, Fangxuan Chu, Ying Li, Tao Yin and Zhipeng Liu
Int. J. Mol. Sci. 2024, 25(9), 4651; https://doi.org/10.3390/ijms25094651 (registering DOI) - 24 Apr 2024
Abstract
Transcranial magneto-acoustic stimulation (TMAS), which is characterized by high spatiotemporal resolution and high penetrability, is a non-invasive neuromodulation technology based on the magnetic–acoustic coupling effect. To reveal the effects of TMAS treatment on amyloid-beta (Aβ) plaque and synaptic plasticity in Alzheimer’s disease, we
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Transcranial magneto-acoustic stimulation (TMAS), which is characterized by high spatiotemporal resolution and high penetrability, is a non-invasive neuromodulation technology based on the magnetic–acoustic coupling effect. To reveal the effects of TMAS treatment on amyloid-beta (Aβ) plaque and synaptic plasticity in Alzheimer’s disease, we conducted a comparative analysis of TMAS and transcranial ultrasound stimulation (TUS) based on acoustic effects in 5xFAD mice and BV2 microglia cells. We found that the TMAS-TUS treatment effectively reduced amyloid plaque loads and plaque-associated neurotoxicity. Additionally, TMAS-TUS treatment ameliorated impairments in long-term memory formation and long-term potentiation. Moreover, TMAS-TUS treatment stimulated microglial proliferation and migration while enhancing the phagocytosis and clearance of Aβ. In 5xFAD mice with induced microglial exhaustion, TMAS-TUS treatment-mediated Aβ plaque reduction, synaptic rehabilitation improvement, and the increase in phospho-AKT levels were diminished. Overall, our study highlights that stimulation of hippocampal microglia by TMAS treatment can induce anti-cognitive impairment effects via PI3K-AKT signaling, providing hope for the development of new strategies for an adjuvant therapy for Alzheimer’s disease.
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(This article belongs to the Section Molecular Neurobiology)
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The Deep Proteomics Approach Identified Extracellular Vesicular Proteins Correlated to Extracellular Matrix in Type One and Two Endometrial Cancer
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Valeria Capaci, Feras Kharrat, Andrea Conti, Emanuela Salviati, Manuela Giovanna Basilicata, Pietro Campiglia, Nour Balasan, Danilo Licastro, Federica Caponnetto, Antonio Paolo Beltrami, Lorenzo Monasta, Federico Romano, Giovanni Di Lorenzo, Giuseppe Ricci and Blendi Ura
Int. J. Mol. Sci. 2024, 25(9), 4650; https://doi.org/10.3390/ijms25094650 (registering DOI) - 24 Apr 2024
Abstract
Among gynecological cancers, endometrial cancer is the most common in developed countries. Extracellular vesicles (EVs) are cell-derived membrane-surrounded vesicles that contain proteins involved in immune response and apoptosis. A deep proteomic approach can help to identify dysregulated extracellular matrix (ECM) proteins in EVs
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Among gynecological cancers, endometrial cancer is the most common in developed countries. Extracellular vesicles (EVs) are cell-derived membrane-surrounded vesicles that contain proteins involved in immune response and apoptosis. A deep proteomic approach can help to identify dysregulated extracellular matrix (ECM) proteins in EVs correlated to key pathways for tumor development. In this study, we used a proteomics approach correlating the two acquisitions—data-dependent acquisition (DDA) and data-independent acquisition (DIA)—on EVs from the conditioned medium of four cell lines identifying 428 ECM proteins. After protein quantification and statistical analysis, we found significant changes in the abundance (p < 0.05) of 67 proteins. Our bioinformatic analysis identified 26 pathways associated with the ECM. Western blotting analysis on 13 patients with type 1 and type 2 EC and 13 endometrial samples confirmed an altered abundance of MMP2. Our proteomics analysis identified the dysregulated ECM proteins involved in cancer growth. Our data can open the path to other studies for understanding the interaction among cancer cells and the rearrangement of the ECM.
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(This article belongs to the Special Issue Integration of Meta-Multi-Omics Data: Unraveling Impact and Therapeutic Potential)
Open AccessReview
Advances in the Synthesis of Biologically Active Quaternary Ammonium Compounds
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Joanna Fedorowicz and Jarosław Sączewski
Int. J. Mol. Sci. 2024, 25(9), 4649; https://doi.org/10.3390/ijms25094649 (registering DOI) - 24 Apr 2024
Abstract
This review provides a comprehensive overview of recent advancements in the design and synthesis of biologically active quaternary ammonium compounds (QACs). The covered scope extends beyond commonly reviewed antimicrobial derivatives to include synthetic agents with antifungal, anticancer, and antiviral properties. Additionally, this review
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This review provides a comprehensive overview of recent advancements in the design and synthesis of biologically active quaternary ammonium compounds (QACs). The covered scope extends beyond commonly reviewed antimicrobial derivatives to include synthetic agents with antifungal, anticancer, and antiviral properties. Additionally, this review highlights examples of quaternary ammonium compounds exhibiting activity against protozoa and herbicidal effects, as well as analgesic and anesthetic derivatives. The article also embraces the quaternary-ammonium-containing cholinesterase inhibitors and muscle relaxants. QACs, marked by their inherent permanent charge, also find widespread usage across diverse domains such as fabric softeners, hair conditioners, detergents, and disinfectants. The effectiveness of QACs hinges greatly on finding the right equilibrium between hydrophilicity and lipophilicity. The ideal length of the alkyl chain varies according to the unique structure of each QAC and its biological settings. It is expected that this review will provide comprehensive data for medicinal and industrial chemists to design and develop novel QAC-based products.
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(This article belongs to the Section Bioactives and Nutraceuticals)
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Steatotic Donor Transplant Livers: Preservation Strategies to Mitigate against Ischaemia-Reperfusion Injury
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Syed Hussain Abbas, Carlo Domenico Lorenzo Ceresa and Joerg-Matthias Pollok
Int. J. Mol. Sci. 2024, 25(9), 4648; https://doi.org/10.3390/ijms25094648 (registering DOI) - 24 Apr 2024
Abstract
Liver transplantation (LT) is the only definitive treatment for end-stage liver disease, yet the UK has seen a 400% increase in liver disease-related deaths since 1970, constrained further by a critical shortage of donor organs. This shortfall has necessitated the use of extended
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Liver transplantation (LT) is the only definitive treatment for end-stage liver disease, yet the UK has seen a 400% increase in liver disease-related deaths since 1970, constrained further by a critical shortage of donor organs. This shortfall has necessitated the use of extended criteria donor organs, including those with evidence of steatosis. The impact of hepatic steatosis (HS) on graft viability remains a concern, particularly for donor livers with moderate to severe steatosis which are highly sensitive to the process of ischaemia-reperfusion injury (IRI) and static cold storage (SCS) leading to poor post-transplantation outcomes. This review explores the pathophysiological predisposition of steatotic livers to IRI, the limitations of SCS, and alternative preservation strategies, including novel organ preservation solutions (OPS) and normothermic machine perfusion (NMP), to mitigate IRI and improve outcomes for steatotic donor livers. By addressing these challenges, the liver transplant community can enhance the utilisation of steatotic donor livers which is crucial in the context of the global obesity crisis and the growing need to expand the donor pool.
Full article
(This article belongs to the Special Issue Ischemia Reperfusion Injury: A Cell Signaling Crossroads and Therapeutics 2.0)
Open AccessArticle
Type II Interleukin-4 Receptor Activation in Basal Breast Cancer Cells Promotes Tumor Progression via Metabolic and Epigenetic Modulation
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Demond Williams, Ebony Hargrove-Wiley, Wendy Bindeman, Daniel Valent, Adam X. Miranda, Jacob Beckstead and Barbara Fingleton
Int. J. Mol. Sci. 2024, 25(9), 4647; https://doi.org/10.3390/ijms25094647 (registering DOI) - 24 Apr 2024
Abstract
Interleukin-4 (IL4) is a Th2 cytokine that can signal through two different receptors, one of which—the type II receptor—is overexpressed by various cancer cells. Previously, we have shown that type II IL4 receptor signaling increases proliferation and metastasis in mouse models of breast
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Interleukin-4 (IL4) is a Th2 cytokine that can signal through two different receptors, one of which—the type II receptor—is overexpressed by various cancer cells. Previously, we have shown that type II IL4 receptor signaling increases proliferation and metastasis in mouse models of breast cancer, as well as increasing glucose and glutamine metabolism. Here, we expand on those findings to determine mechanistically how IL4 signaling links glucose metabolism and histone acetylation to drive proliferation in the context of triple-negative breast cancer (TNBC). We used a combination of cellular, biochemical, and genomics approaches to interrogate TNBC cell lines, which represent a cancer type where high expression of the type II IL4 receptor is linked to reduced survival. Our results indicate that type II IL4 receptor activation leads to increased glucose uptake, Akt and ACLY activation, and histone acetylation in TNBC cell lines. Inhibition of glucose uptake through the deletion of Glut1 ablates IL4-induced proliferation. Additionally, pharmacological inhibition of histone acetyltransferase P300 attenuates IL4-mediated gene expression and proliferation in vitro. Our work elucidates a role for type II IL4 receptor signaling in promoting TNBC progression, and highlights type II IL4 signaling, as well as histone acetylation, as possible targets for therapy.
Full article
(This article belongs to the Special Issue Recent Advances in Breast Cancer Research 2.0)
Open AccessArticle
Process Intensification for Enhanced Fluoride Removal and Recovery as Calcium Fluoride Using a Fluidized Bed Reactor
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Arindam Sinharoy, Ga-Young Lee and Chong-Min Chung
Int. J. Mol. Sci. 2024, 25(9), 4646; https://doi.org/10.3390/ijms25094646 - 24 Apr 2024
Abstract
This study explored the feasibility of fluoride removal from simulated semiconductor industry wastewater and its recovery as calcium fluoride using fluidized bed crystallization. The continuous reactor showed the best performance (>90% fluoride removal and >95% crystallization efficiency) at a calcium-to-fluoride ratio of 0.6
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This study explored the feasibility of fluoride removal from simulated semiconductor industry wastewater and its recovery as calcium fluoride using fluidized bed crystallization. The continuous reactor showed the best performance (>90% fluoride removal and >95% crystallization efficiency) at a calcium-to-fluoride ratio of 0.6 within the first 40 days of continuous operation. The resulting particle size increased by more than double during this time, along with a 36% increase in the seed bed height, indicating the deposition of CaF2 onto the silica seed. The SEM-EDX analysis showed the size and shape of the crystals formed, along with the presence of a high amount of Ca-F ions. The purity of the CaF2 crystals was determined to be 91.1% though ICP-OES analysis. Following the continuous experiment, different process improvement strategies were explored. The addition of an excess amount of calcium resulted in the removal of an additional 6% of the fluoride; however, compared to this single-stage process, a two-stage approach was found to be a better strategy to achieve a low effluent concentration of fluoride. The fluoride removal reached 94% with this two-stage approach under the optimum conditions of 4 + 1 h HRT combinations and a [Ca2+]/[F−] ratio of 0.55 and 0.7 for the two reactors, respectively. CFD simulation showed the impact of the inlet diameter, bottom-angle shape, and width-to-height ratio of the reactor on the mixing inside the reactor and the possibility of further improvement in the reactor performance by optimizing the FBR configuration.
Full article
(This article belongs to the Section Biochemistry)
Open AccessReview
The Role of Phospholipid Alterations in Mitochondrial and Brain Dysfunction after Cardiac Arrest
by
Rishabh C. Choudhary, Cyrus E. Kuschner, Jacob Kazmi, Liam Mcdevitt, Blanca B. Espin, Mohammed Essaihi, Mitsuaki Nishikimi, Lance B. Becker and Junhwan Kim
Int. J. Mol. Sci. 2024, 25(9), 4645; https://doi.org/10.3390/ijms25094645 - 24 Apr 2024
Abstract
The human brain possesses three predominate phospholipids, phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS), which account for approximately 35–40%, 35–40%, and 20% of the brain’s phospholipids, respectively. Mitochondrial membranes are relatively diverse, containing the aforementioned PC, PE, and PS, as well as phosphatidylinositol
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The human brain possesses three predominate phospholipids, phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS), which account for approximately 35–40%, 35–40%, and 20% of the brain’s phospholipids, respectively. Mitochondrial membranes are relatively diverse, containing the aforementioned PC, PE, and PS, as well as phosphatidylinositol (PI) and phosphatidic acid (PA); however, cardiolipin (CL) and phosphatidylglycerol (PG) are exclusively present in mitochondrial membranes. These phospholipid interactions play an essential role in mitochondrial fusion and fission dynamics, leading to the maintenance of mitochondrial structural and signaling pathways. The essential nature of these phospholipids is demonstrated through the inability of mitochondria to tolerate alteration in these specific phospholipids, with changes leading to mitochondrial damage resulting in neural degeneration. This review will emphasize how the structure of phospholipids relates to their physiologic function, how their metabolism facilitates signaling, and the role of organ- and mitochondria-specific phospholipid compositions. Finally, we will discuss the effects of global ischemia and reperfusion on organ- and mitochondria-specific phospholipids alongside the novel therapeutics that may protect against injury.
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(This article belongs to the Special Issue Advances in Molecular Research of Lipid Mediators)
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Characterization of Human B Cell Hematological Malignancies Using Protein-Based Approaches
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Cristina Jiménez, Alba Garrote-de-Barros, Carlos López-Portugués, María Hernández-Sánchez and Paula Díez
Int. J. Mol. Sci. 2024, 25(9), 4644; https://doi.org/10.3390/ijms25094644 - 24 Apr 2024
Abstract
The maturation of B cells is a complex, multi-step process. During B cell differentiation, errors can occur, leading to the emergence of aberrant versions of B cells that, finally, constitute a malignant tumor. These B cell malignancies are classified into three main groups:
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The maturation of B cells is a complex, multi-step process. During B cell differentiation, errors can occur, leading to the emergence of aberrant versions of B cells that, finally, constitute a malignant tumor. These B cell malignancies are classified into three main groups: leukemias, myelomas, and lymphomas, the latter being the most heterogeneous type. Since their discovery, multiple biological studies have been performed to characterize these diseases, aiming to define their specific features and determine potential biomarkers for diagnosis, stratification, and prognosis. The rise of advanced -omics approaches has significantly contributed to this end. Notably, proteomics strategies appear as promising tools to comprehensively profile the final molecular effector of these cells. In this narrative review, we first introduce the main B cell malignancies together with the most relevant proteomics approaches. Then, we describe the core studies conducted in the field and their main findings and, finally, we evaluate the advantages and drawbacks of flow cytometry, mass cytometry, and mass spectrometry for the profiling of human B cell disorders.
Full article
(This article belongs to the Special Issue Proteomics and Its Applications in Human Biology)
Open AccessReview
Tyrosine Hydroxylase Inhibitors and Dopamine Receptor Agonists Combination Therapy for Parkinson’s Disease
by
Ling Xiao Yi, Eng King Tan and Zhi Dong Zhou
Int. J. Mol. Sci. 2024, 25(9), 4643; https://doi.org/10.3390/ijms25094643 - 24 Apr 2024
Abstract
There are currently no disease-modifying therapies for Parkinson’s disease (PD), a progressive neurodegenerative disorder associated with dopaminergic neuronal loss. There is increasing evidence that endogenous dopamine (DA) can be a pathological factor in neurodegeneration in PD. Tyrosine hydroxylase (TH) is the key rate-limiting
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There are currently no disease-modifying therapies for Parkinson’s disease (PD), a progressive neurodegenerative disorder associated with dopaminergic neuronal loss. There is increasing evidence that endogenous dopamine (DA) can be a pathological factor in neurodegeneration in PD. Tyrosine hydroxylase (TH) is the key rate-limiting enzyme for DA generation. Drugs that inhibit TH, such as alpha-methyltyrosine (α-MT), have recently been shown to protect against neurodegeneration in various PD models. DA receptor agonists can activate post-synaptic DA receptors to alleviate DA-deficiency-induced PD symptoms. However, DA receptor agonists have no therapeutic effects against neurodegeneration. Thus, a combination therapy with DA receptor agonists plus TH inhibitors may be an attractive therapeutic approach. TH inhibitors can protect and promote the survival of remaining dopaminergic neurons in PD patients’ brains, whereas DA receptor agonists activate post-synaptic DA receptors to alleviate PD symptoms. Additionally, other PD drugs, such as N-acetylcysteine (NAC) and anticholinergic drugs, may be used as adjunctive medications to improve therapeutic effects. This multi-drug cocktail may represent a novel strategy to protect against progressive dopaminergic neurodegeneration and alleviate PD disease progression.
Full article
(This article belongs to the Special Issue The Role of Dopamine Neurotransmitters in Neurological Diseases: New Sight)
Open AccessArticle
A Multi-Faceted Binding Assessment of Aptamers Targeting the SARS-CoV-2 Spike Protein
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Laia Civit, Nima Moradzadeh, Anna Jonczyk, Patrick Neckermann, Benedikt Asbach, David Peterhoff, Ralf Wagner, Michael Famulok, Günter Mayer, Jørgen Kjems and Julián Valero
Int. J. Mol. Sci. 2024, 25(9), 4642; https://doi.org/10.3390/ijms25094642 - 24 Apr 2024
Abstract
The COVID-19 pandemic has underscored the critical need for the advancement of diagnostic and therapeutic platforms. These platforms rely on the rapid development of molecular binders that should facilitate surveillance and swift intervention against viral infections. In this study, we have evaluated by
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The COVID-19 pandemic has underscored the critical need for the advancement of diagnostic and therapeutic platforms. These platforms rely on the rapid development of molecular binders that should facilitate surveillance and swift intervention against viral infections. In this study, we have evaluated by three independent research groups the binding characteristics of various published RNA and DNA aptamers targeting the spike protein of the SARS-CoV-2 virus. For this comparative analysis, we have employed different techniques such as biolayer interferometry (BLI), enzyme-linked oligonucleotide assay (ELONA), and flow cytometry. Our data show discrepancies in the reported specificity and affinity among several of the published aptamers and underline the importance of standardized methods, the impact of biophysical techniques, and the controls used for aptamer characterization. We expect our results to contribute to the selection and application of suitable aptamers for the detection of SARS-CoV-2.
Full article
(This article belongs to the Special Issue Aptamers: Functional and Structural Studies)
Open AccessArticle
The Bifunctional Effects of Lactoferrin (LFcinB11) in Inhibiting Neural Cell Adhesive Molecule (NCAM) Polysialylation and the Release of Neutrophil Extracellular Traps (NETs)
by
Bo Lu, Si-Ming Liao, Shi-Jie Liang, Li-Xin Peng, Jian-Xiu Li, Xue-Hui Liu, Ri-Bo Huang and Guo-Ping Zhou
Int. J. Mol. Sci. 2024, 25(9), 4641; https://doi.org/10.3390/ijms25094641 - 24 Apr 2024
Abstract
The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM) is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and aggressive clinical status. Thus, it is important to select a proper drug to block
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The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM) is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and aggressive clinical status. Thus, it is important to select a proper drug to block tumor cell migration during clinical treatment. In this study, we proposed that lactoferrin (LFcinB11) may be a better candidate for inhibiting NCAM polysialylation when compared with CMP and low-molecular-weight heparin (LMWH), which were determined based on our NMR studies. Furthermore, neutrophil extracellular traps (NETs) represent the most dramatic stage in the cell death process, and the release of NETs is related to the pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis, and vascular disorders. In this study, the molecular mechanisms involved in the inhibition of NET release using LFcinB11 as an inhibitor were also determined. Based on these results, LFcinB11 is proposed as being a bifunctional inhibitor for inhibiting both NCAM polysialylation and the release of NETs.
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(This article belongs to the Special Issue Mechanisms of Small Molecule Inhibitors Targeting Cancer)
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Open AccessArticle
Dolutegravir and Folic Acid Interaction during Neural System Development in Zebrafish Embryos
by
Daniela Zizioli, Eugenia Quiros-Roldan, Sara Ferretti, Luca Mignani, Giorgio Tiecco, Eugenio Monti, Francesco Castelli and Isabella Zanella
Int. J. Mol. Sci. 2024, 25(9), 4640; https://doi.org/10.3390/ijms25094640 - 24 Apr 2024
Abstract
Dolutegravir (DTG) is one of the most prescribed antiretroviral drugs for treating people with HIV infection, including women of child-bearing potential or pregnant. Nonetheless, neuropsychiatric symptoms are frequently reported. Early reports suggested that, probably in relation to folic acid (FA) shortage, DTG may
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Dolutegravir (DTG) is one of the most prescribed antiretroviral drugs for treating people with HIV infection, including women of child-bearing potential or pregnant. Nonetheless, neuropsychiatric symptoms are frequently reported. Early reports suggested that, probably in relation to folic acid (FA) shortage, DTG may induce neural tube defects in infants born to women taking the drug during pregnancy. Subsequent reports did not definitively confirm these findings. Recent studies in animal models have highlighted the association between DTG exposure in utero and congenital anomalies, and an increased risk of neurologic abnormalities in children exposed during in utero life has been reported. Underlying mechanisms for DTG-related neurologic symptoms and congenital anomalies are not fully understood. We aimed to deepen our knowledge on the neurodevelopmental effects of DTG exposure and further explore the protective role of FA by the use of zebrafish embryos. We treated embryos at 4 and up to 144 h post fertilization (hpf) with a subtherapeutic DTG concentration (1 μM) and observed the disruption of the anterior–posterior axis and several morphological malformations in the developing brain that were both prevented by pre-exposure (2 hpf) and rescued by post-exposure (10 hpf) with FA. By whole-mount in situ hybridization with riboprobes for genes that are crucial during the early phases of neurodevelopment (ntl, pax2a, ngn1, neurod1) and by in vivo visualization of the transgenic Tg(ngn1:EGFP) zebrafish line, we found that DTG induced severe neurodevelopmental defects over time in most regions of the nervous system (notochord, midbrain–hindbrain boundary, eye, forebrain, midbrain, hindbrain, spinal cord) that were mostly but not completely rescued by FA supplementation. Of note, we observed the disruption of ngn1 expression in the dopaminergic regions of the developing forebrain, spinal cord neurons and spinal motor neuron projections, with the depletion of the tyrosine hydroxylase (TH)+ dopaminergic neurons of the dorsal diencephalon and the strong reduction in larvae locomotion. Our study further supports previous evidence that DTG can interfere with FA pathways in the developing brain but also provides new insights regarding the mechanisms involved in the increased risk of DTG-associated fetal neurodevelopmental defects and adverse neurologic outcomes in in utero exposed children, suggesting the impairment of dopaminergic pathways.
Full article
(This article belongs to the Special Issue Animal Research Model for Neurological Diseases)
Open AccessReview
Chronic Traumatic Encephalopathy as the Course of Alzheimer’s Disease
by
Magdalena Pszczołowska, Kamil Walczak, Weronika Miśków, Katarzyna Antosz, Joanna Batko, Donata Kurpas and Jerzy Leszek
Int. J. Mol. Sci. 2024, 25(9), 4639; https://doi.org/10.3390/ijms25094639 - 24 Apr 2024
Abstract
This editorial investigates chronic traumatic encephalopathy (CTE) as a course of Alzheimer’s disease (AD). CTE is a debilitating neurodegenerative disease that is the result of repeated mild traumatic brain injury (TBI). Many epidemiological studies show that experiencing a TBI in early or middle
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This editorial investigates chronic traumatic encephalopathy (CTE) as a course of Alzheimer’s disease (AD). CTE is a debilitating neurodegenerative disease that is the result of repeated mild traumatic brain injury (TBI). Many epidemiological studies show that experiencing a TBI in early or middle life is associated with an increased risk of dementia later in life. Chronic traumatic encephalopathy (CTE) and Alzheimer’s disease (AD) present a series of similar neuropathological features that were investigated in this work like recombinant tau into filaments or the accumulation and aggregation of Aβ protein. However, these two conditions differ from each other in brain–blood barrier damage. The purpose of this review was to evaluate information about CTE and AD from various articles, focusing especially on new therapeutic possibilities for the improvement in cognitive skills.
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(This article belongs to the Special Issue Traumatic Brain Injury/Chronic Traumatic Encephalopathy as Cause of Alzheimer’s Disease: Physics and Molecular Biology in the Genesis of Neurodegeneration?)
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Open AccessArticle
Integrative and Conjugative Elements and Prophage DNA as Carriers of Resistance Genes in Erysipelothrix rhusiopathiae Strains from Domestic Geese in Poland
by
Marta Dec, Aldert Zomer, John Webster, Tomasz Nowak, Dagmara Stępień-Pyśniak and Renata Urban-Chmiel
Int. J. Mol. Sci. 2024, 25(9), 4638; https://doi.org/10.3390/ijms25094638 - 24 Apr 2024
Abstract
Goose erysipelas is a serious problem in waterfowl breeding in Poland. However, knowledge of the characteristics of Erysipelothrix rhusiopathiae strains causing this disease is limited. In this study, the antimicrobial susceptibility and serotypes of four E. rhusiopathiae strains from domestic geese were determined,
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Goose erysipelas is a serious problem in waterfowl breeding in Poland. However, knowledge of the characteristics of Erysipelothrix rhusiopathiae strains causing this disease is limited. In this study, the antimicrobial susceptibility and serotypes of four E. rhusiopathiae strains from domestic geese were determined, and their whole-genome sequences (WGSs) were analyzed to detect resistance genes, integrative and conjugative elements (ICEs), and prophage DNA. Sequence type and the presence of resistance genes and transposons were compared with 363 publicly available E. rhusiopathiae strains, as well as 13 strains of other Erysipelothrix species. Four strains tested represented serotypes 2 and 5 and the MLST groups ST 4, 32, 242, and 243. Their assembled circular genomes ranged from 1.8 to 1.9 kb with a GC content of 36–37%; a small plasmid was detected in strain 1023. Strains 1023 and 267 were multidrug-resistant. The resistance genes detected in the genome of strain 1023 were erm47, tetM, and lsaE-lnuB-ant(6)-Ia-spw cluster, while strain 267 contained the tetM and ermB genes. Mutations in the gyrA gene were detected in both strains. The tetM gene was embedded in a Tn916-like transposon, which in strain 1023, together with the other resistance genes, was located on a large integrative and conjugative-like element of 130 kb designated as ICEEr1023. A minor integrative element of 74 kb was identified in strain 1012 (ICEEr1012). This work contributes to knowledge about the characteristics of E. rhusiopathiae bacteria and, for the first time, reveals the occurrence of erm47 and ermB resistance genes in strains of this species. Phage infection appears to be responsible for the introduction of the ermB gene into the genome of strain 267, while ICEs most likely play a key role in the spread of the other resistance genes identified in E. rhusiopathiae.
Full article
(This article belongs to the Special Issue Antibiotic Resistance: Appearance, Evolution, and Spread 2.0)
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