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
Analysing the Cyanobacterial PipX Interaction Network Using NanoBiT Complementation in Synechococcus elongatus PCC7942
Int. J. Mol. Sci. 2024, 25(9), 4702; https://doi.org/10.3390/ijms25094702 (registering DOI) - 25 Apr 2024
Abstract
The conserved cyanobacterial protein PipX is part of a complex interaction network with regulators involved in essential processes that include metabolic homeostasis and ribosome assembly. Because PipX interactions depend on the relative levels of their different partners and of the effector molecules binding
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The conserved cyanobacterial protein PipX is part of a complex interaction network with regulators involved in essential processes that include metabolic homeostasis and ribosome assembly. Because PipX interactions depend on the relative levels of their different partners and of the effector molecules binding to them, in vivo studies are required to understand the physiological significance and contribution of environmental factors to the regulation of PipX complexes. Here, we have used the NanoBiT complementation system to analyse the regulation of complex formation in Synechococcus elongatus PCC 7942 between PipX and each of its two best-characterized partners, PII and NtcA. Our results confirm previous in vitro analyses on the regulation of PipX-PII and PipX-NtcA complexes by 2-oxoglutarate and on the regulation of PipX-PII by the ATP/ADP ratio, showing the disruption of PipX-NtcA complexes due to increased levels of ADP-bound PII in Synechococcus elongatus. The demonstration of a positive role of PII on PipX-NtcA complexes during their initial response to nitrogen starvation or the impact of a PipX point mutation on the activity of PipX-PII and PipX-NtcA reporters are further indications of the sensitivity of the system. This study reveals additional regulatory complexities in the PipX interaction network, opening a path for future research on cyanobacteria.
Full article
(This article belongs to the Special Issue Advances in Protein-Protein Interactions 2.0)
Open AccessArticle
How to Personalize General Anesthesia—A Prospective Theoretical Approach to Conformational Changes of Halogenated Anesthetics in Fire Smoke Poisoning
by
Flavius Nicușor Truicu, Roni Octavian Damian, Mihai Alexandru Butoi, Vlad Ionuț Belghiru, Luciana Teodora Rotaru, Monica Puticiu and Renata Maria Văruț
Int. J. Mol. Sci. 2024, 25(9), 4701; https://doi.org/10.3390/ijms25094701 (registering DOI) - 25 Apr 2024
Abstract
Smoke intoxication is a central event in mass burn incidents, and toxic smoke acts at different levels of the body, blocking breathing and oxygenation. The majority of these patients require early induction of anesthesia to preserve vital functions. We studied the influence of
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Smoke intoxication is a central event in mass burn incidents, and toxic smoke acts at different levels of the body, blocking breathing and oxygenation. The majority of these patients require early induction of anesthesia to preserve vital functions. We studied the influence of hemoglobin (HMG) and myoglobin (MGB) blockade by hydrochloric acid (HCl) in an interaction model with gaseous anesthetics using molecular docking techniques. In the next part of the study, molecular dynamics (MD) simulations were performed on the top-scoring ligand–receptor complexes to investigate the stability of the ligand–receptor complexes and the interactions between ligands and receptors in more detail. Through docking analysis, we observed that hemoglobin creates more stable complexes with anesthetic gases than myoglobin. Intoxication with gaseous hydrochloric acid produces conformational and binding energy changes of anesthetic gases to the substrate (both the pathway and the binding site), the most significant being recorded in the case of desflurane and sevoflurane, while for halothane and isoflurane, they remain unchanged. According to our theoretical model, the selection of anesthetic agents for patients affected by fire smoke containing hydrochloric acid is critical to ensure optimal anesthetic effects. In this regard, our model suggests that halothane and isoflurane are the most suitable choices for predicting the anesthetic effects in such patients when compared to sevoflurane and desflurane.
Full article
(This article belongs to the Special Issue Molecular Toxicology of New Drugs: New Insights)
Open AccessArticle
Genome-Wide Identification, Phylogenetic and Expression Analysis of Expansin Gene Family in Medicago sativa L
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Yajing Li, Yangyang Zhang, Jing Cui, Xue Wang, Mingna Li, Lili Zhang and Junmei Kang
Int. J. Mol. Sci. 2024, 25(9), 4700; https://doi.org/10.3390/ijms25094700 (registering DOI) - 25 Apr 2024
Abstract
Expansins, a class of cell-wall-loosening proteins that regulate plant growth and stress resistance, have been studied in a variety of plant species. However, little is known about the Expansins present in alfalfa (Medicago sativa L.) due to the complexity of its tetraploidy.
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Expansins, a class of cell-wall-loosening proteins that regulate plant growth and stress resistance, have been studied in a variety of plant species. However, little is known about the Expansins present in alfalfa (Medicago sativa L.) due to the complexity of its tetraploidy. Based on the alfalfa (cultivar “XinjiangDaye”) reference genome, we identified 168 Expansin members (MsEXPs). Phylogenetic analysis showed that MsEXPs consist of four subfamilies: MsEXPAs (123), MsEXPBs (25), MsEXLAs (2), and MsEXLBs (18). MsEXPAs, which account for 73.2% of MsEXPs, and are divided into twelve groups (EXPA-I–EXPA-XII). Of these, EXPA-XI members are specific to Medicago trunctula and alfalfa. Gene composition analysis revealed that the members of each individual subfamily shared a similar structure. Interestingly, about 56.3% of the cis-acting elements were predicted to be associated with abiotic stress, and the majority were MYB- and MYC-binding motifs, accounting for 33.9% and 36.0%, respectively. Our short-term treatment (≤24 h) with NaCl (200 mM) or PEG (polyethylene glycol, 15%) showed that the transcriptional levels of 12 MsEXPs in seedlings were significantly altered at the tested time point(s), indicating that MsEXPs are osmotic-responsive. These findings imply the potential functions of MsEXPs in alfalfa adaptation to high salinity and/or drought. Future studies on MsEXP expression profiles under long-term (>24 h) stress treatment would provide valuable information on their involvement in the response of alfalfa to abiotic stress.
Full article
(This article belongs to the Section Molecular Genetics and Genomics)
Open AccessReview
Anti-Obesity Therapeutic Targets Studied In Silico and In Vivo: A Systematic Review
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Wendjilla F. de Medeiros, Ana Francisca T. Gomes, Ana Júlia F. C. Aguiar, Jaluza Luana C. de Queiroz, Ingrid Wilza L. Bezerra, Juliana Kelly da Silva-Maia, Grasiela Piuvezam and Ana Heloneida de A. Morais
Int. J. Mol. Sci. 2024, 25(9), 4699; https://doi.org/10.3390/ijms25094699 (registering DOI) - 25 Apr 2024
Abstract
In the age of information technology and the additional computational search tools and software available, this systematic review aimed to identify potential therapeutic targets for obesity, evaluated in silico and subsequently validated in vivo. The systematic review was initially guided by the research
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In the age of information technology and the additional computational search tools and software available, this systematic review aimed to identify potential therapeutic targets for obesity, evaluated in silico and subsequently validated in vivo. The systematic review was initially guided by the research question “What therapeutic targets have been used in in silico analysis for the treatment of obesity?” and structured based on the acronym PECo (P, problem; E, exposure; Co, context). The systematic review protocol was formulated and registered in PROSPERO (CRD42022353808) in accordance with the Preferred Reporting Items Checklist for Systematic Review and Meta-Analysis Protocols (PRISMA-P), and the PRISMA was followed for the systematic review. The studies were selected according to the eligibility criteria, aligned with PECo, in the following databases: PubMed, ScienceDirect, Scopus, Web of Science, BVS, and EMBASE. The search strategy yielded 1142 articles, from which, based on the evaluation criteria, 12 were included in the systematic review. Only seven these articles allowed the identification of both in silico and in vivo reassessed therapeutic targets. Among these targets, five were exclusively experimental, one was exclusively theoretical, and one of the targets presented an experimental portion and a portion obtained by modeling. The predominant methodology used was molecular docking and the most studied target was Human Pancreatic Lipase (HPL) (n = 4). The lack of methodological details resulted in more than 50% of the papers being categorized with an “unclear risk of bias” across eight out of the eleven evaluated criteria. From the current systematic review, it seems evident that integrating in silico methodologies into studies of potential drug targets for the exploration of new therapeutic agents provides an important tool, given the ongoing challenges in controlling obesity.
Full article
(This article belongs to the Special Issue Anti-obesity Drug Discovery)
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Open AccessArticle
Pure-Shift-Based Proton Magnetic Resonance Spectroscopy for High-Resolution Studies of Biological Samples
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Haolin Zhan, Yulei Chen, Yinping Cui, Yunsong Zeng, Xiaozhen Feng, Chunhua Tan, Chengda Huang, Enping Lin, Yuqing Huang and Zhong Chen
Int. J. Mol. Sci. 2024, 25(9), 4698; https://doi.org/10.3390/ijms25094698 (registering DOI) - 25 Apr 2024
Abstract
Proton magnetic resonance spectroscopy (1H MRS) presents a powerful tool for revealing molecular-level metabolite information, complementary to the anatomical insight delivered by magnetic resonance imaging (MRI), thus playing a significant role in in vivo/in vitro biological studies. However, its further applications
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Proton magnetic resonance spectroscopy (1H MRS) presents a powerful tool for revealing molecular-level metabolite information, complementary to the anatomical insight delivered by magnetic resonance imaging (MRI), thus playing a significant role in in vivo/in vitro biological studies. However, its further applications are generally confined by spectral congestion caused by numerous biological metabolites contained within the limited proton frequency range. Herein, we propose a pure-shift-based 1H localized MRS method as a proof of concept for high-resolution studies of biological samples. Benefitting from the spectral simplification from multiplets to singlet peaks, this method addresses the challenge of spectral congestion encountered in conventional MRS experiments and facilitates metabolite analysis from crowded NMR resonances. The performance of the proposed pure-shift 1H MRS method is demonstrated on different kinds of samples, including brain metabolite phantom and in vitro biological samples of intact pig brain tissue and grape tissue, using a 7.0 T animal MRI scanner. This proposed MRS method is readily implemented in common commercial NMR/MRI instruments because of its generally adopted pulse-sequence modules. Therefore, this study takes a meaningful step for MRS studies toward potential applications in metabolite analysis and disease diagnosis.
Full article
(This article belongs to the Special Issue Advances in Molecular and Cellular Imaging, Microscopy, and Biomedical Spectroscopy)
Open AccessReview
HIV-Associated Neurocognitive Disorder: A Look into Cellular and Molecular Pathology
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Landon John-Patrick Thompson, Jessica Genovese, Zhenzi Hong, Meera Vir Singh and Vir Bahadur Singh
Int. J. Mol. Sci. 2024, 25(9), 4697; https://doi.org/10.3390/ijms25094697 (registering DOI) - 25 Apr 2024
Abstract
Despite combined antiretroviral therapy (cART) limiting HIV replication to undetectable levels in the blood, people living with HIV continue to experience HIV-associated neurocognitive disorder (HAND). HAND is associated with neurocognitive impairment, including motor impairment, and memory loss. HIV has been detected in the
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Despite combined antiretroviral therapy (cART) limiting HIV replication to undetectable levels in the blood, people living with HIV continue to experience HIV-associated neurocognitive disorder (HAND). HAND is associated with neurocognitive impairment, including motor impairment, and memory loss. HIV has been detected in the brain within 8 days of estimated exposure and the mechanisms for this early entry are being actively studied. Once having entered into the central nervous system (CNS), HIV degrades the blood–brain barrier through the production of its gp120 and Tat proteins. These proteins are directly toxic to endothelial cells and neurons, and propagate inflammatory cytokines by the activation of immune cells and dysregulation of tight junction proteins. The BBB breakdown is associated with the progression of neurocognitive disease. One of the main hurdles for treatment for HAND is the latent pool of cells, which are insensitive to cART and prolong inflammation by harboring the provirus in long-lived cells that can reactivate, causing damage. Multiple strategies are being studied to combat the latent pool and HAND; however, clinically, these approaches have been insufficient and require further revisions. The goal of this paper is to aggregate the known mechanisms and challenges associated with HAND.
Full article
(This article belongs to the Special Issue Mechanisms of Neurotoxicity)
Open AccessReview
Brain–Periphery Interactions in Huntington’s Disease: Mediators and Lifestyle Interventions
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Johannes Burtscher, Barbara Strasser, Giuseppe Pepe, Martin Burtscher, Martin Kopp, Alba Di Pardo, Vittorio Maglione and Andy V. Khamoui
Int. J. Mol. Sci. 2024, 25(9), 4696; https://doi.org/10.3390/ijms25094696 (registering DOI) - 25 Apr 2024
Abstract
Prominent pathological features of Huntington’s disease (HD) are aggregations of mutated Huntingtin protein (mHtt) in the brain and neurodegeneration, which causes characteristic motor (such as chorea and dystonia) and non-motor symptoms. However, the numerous systemic and peripheral deficits in HD have gained increasing
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Prominent pathological features of Huntington’s disease (HD) are aggregations of mutated Huntingtin protein (mHtt) in the brain and neurodegeneration, which causes characteristic motor (such as chorea and dystonia) and non-motor symptoms. However, the numerous systemic and peripheral deficits in HD have gained increasing attention recently, since those factors likely modulate disease progression, including brain pathology. While whole-body metabolic abnormalities and organ-specific pathologies in HD have been relatively well described, the potential mediators of compromised inter-organ communication in HD have been insufficiently characterized. Therefore, we applied an exploratory literature search to identify such mediators. Unsurprisingly, dysregulation of inflammatory factors, circulating mHtt, and many other messenger molecules (hormones, lipids, RNAs) were found that suggest impaired inter-organ communication, including of the gut–brain and muscle–brain axis. Based on these findings, we aimed to assess the risks and potentials of lifestyle interventions that are thought to improve communication across these axes: dietary strategies and exercise. We conclude that appropriate lifestyle interventions have great potential to reduce symptoms and potentially modify disease progression (possibly via improving inter-organ signaling) in HD. However, impaired systemic metabolism and peripheral symptoms warrant particular care in the design of dietary and exercise programs for people with HD.
Full article
(This article belongs to the Special Issue Huntington’s Disease: Molecular Advances in Therapeutics)
Open AccessArticle
Distinct Driver Pathway Enrichments and a High Prevalence of TSC2 Mutations in Right Colon Cancer in Chile: A Preliminary Comparative Analysis
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Camilo Tapia-Valladares, Guillermo Valenzuela, Evelin González, Ignacio Maureira, Jessica Toro, Matías Freire, Gonzalo Sepúlveda-Hermosilla, Diego Ampuero, Alejandro Blanco, Iván Gallegos, Fernanda Morales, José I. Erices, Olga Barajas, Mónica Ahumada, Héctor R. Contreras, Jaime González, Ricardo Armisén and Katherine Marcelain
Int. J. Mol. Sci. 2024, 25(9), 4695; https://doi.org/10.3390/ijms25094695 (registering DOI) - 25 Apr 2024
Abstract
Colorectal cancer (CRC) is the second leading cause of cancer deaths globally. While ethnic differences in driver gene mutations have been documented, the South American population remains understudied at the genomic level, despite facing a rising burden of CRC. We analyzed tumors of
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Colorectal cancer (CRC) is the second leading cause of cancer deaths globally. While ethnic differences in driver gene mutations have been documented, the South American population remains understudied at the genomic level, despite facing a rising burden of CRC. We analyzed tumors of 40 Chilean CRC patients (Chp) using next-generation sequencing and compared them to data from mainly Caucasian cohorts (TCGA and MSK-IMPACT). We identified 388 mutations in 96 out of 135 genes, with TP53 (45%), KRAS (30%), PIK3CA (22.5%), ATM (20%), and POLE (20%) being the most frequently mutated. TSC2 mutations were associated with right colon cancer (44.44% in RCRC vs. 6.45% in LCRC, p-value = 0.016), and overall frequency was higher compared to TCGA (p-value = 1.847 × 10−5) and MSK-IMPACT cohorts (p-value = 3.062 × 10−2). Limited sample size restricts definitive conclusions, but our data suggest potential differences in driver mutations for Chilean patients, being that the RTK-RAS oncogenic pathway is less affected and the PI3K pathway is more altered in Chp compared to TCGA (45% vs. 25.56%, respectively). The prevalence of actionable pathways and driver mutations can guide therapeutic choices, but can also impact treatment effectiveness. Thus, these findings warrant further investigation in larger Chilean cohorts to confirm these initial observations. Understanding population-specific driver mutations can guide the development of precision medicine programs for CRC patients.
Full article
(This article belongs to the Special Issue Cancer Genomics and Precision Oncology)
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Open AccessArticle
Single-Cell Transcriptional Profile Construction of Rat Pituitary Glands before and after Sexual Maturation and Identification of Novel Marker Spp1 in Gonadotropes
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Qing-Hua Huang, Guo-Kun Zhao, Hao-Qi Wang, Fan-Hao Wei, Jin-Yu Zhang, Jia-Bao Zhang, Fei Gao and Bao Yuan
Int. J. Mol. Sci. 2024, 25(9), 4694; https://doi.org/10.3390/ijms25094694 (registering DOI) - 25 Apr 2024
Abstract
The mammalian pituitary gland drives highly conserved physiological processes such as somatic cell growth, pubertal transformation, fertility, and metabolism by secreting a variety of hormones. Recently, single-cell transcriptomics techniques have been used in pituitary gland research. However, more studies have focused on adult
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The mammalian pituitary gland drives highly conserved physiological processes such as somatic cell growth, pubertal transformation, fertility, and metabolism by secreting a variety of hormones. Recently, single-cell transcriptomics techniques have been used in pituitary gland research. However, more studies have focused on adult pituitary gland tissues from different species or different sexes, and no research has yet resolved cellular differences in pituitary gland tissue before and after sexual maturation. Here, we identified a total of 15 cell clusters and constructed single-cell transcriptional profiles of rats before and after sexual maturation. Furthermore, focusing on the gonadotrope cluster, 106 genes were found to be differentially expressed before and after sexual maturation. It was verified that Spp1, which is specifically expressed in gonadotrope cells, could serve as a novel marker for this cell cluster and has a promotional effect on the synthesis and secretion of follicle-stimulating hormone. The results provide a new resource for further resolving the regulatory mechanism of pituitary gland development and pituitary hormone synthesis and secretion.
Full article
(This article belongs to the Special Issue Molecular Studies in Endocrinology and Reproductive Biology)
Open AccessArticle
Design and Synthesis of 1,3-Diarylpyrazoles and Investigation of Their Cytotoxicity and Antiparasitic Profile
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Murat Bozdag, Freke Mertens, An Matheeussen, Natascha Van Pelt, Kenn Foubert, Nina Hermans, Guido R. Y. De Meyer, Koen Augustyns, Wim Martinet, Guy Caljon and Pieter Van der Veken
Int. J. Mol. Sci. 2024, 25(9), 4693; https://doi.org/10.3390/ijms25094693 (registering DOI) - 25 Apr 2024
Abstract
Herein, we report a series of 1,3-diarylpyrazoles that are analogues of compound 26/HIT 8. We previously identified this molecule as a ‘hit’ during a high-throughput screening campaign for autophagy inducers. A variety of synthetic strategies were utilized to modify the 1,3-diarylpyrazole core
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Herein, we report a series of 1,3-diarylpyrazoles that are analogues of compound 26/HIT 8. We previously identified this molecule as a ‘hit’ during a high-throughput screening campaign for autophagy inducers. A variety of synthetic strategies were utilized to modify the 1,3-diarylpyrazole core at its 1-, 3-, and 4-position. Compounds were assessed in vitro to identify their cytotoxicity properties. Of note, several compounds in the series displayed relevant cytotoxicity, which warrants scrutiny while interpreting biological activities that have been reported for structurally related molecules. In addition, antiparasitic activities were recorded against a range of human-infective protozoa, including Trypanosoma cruzi, T. brucei rhodesiense, and Leishmania infantum. The most interesting compounds displayed low micromolar whole-cell potencies against individual or several parasitic species, while lacking cytotoxicity against human cells.
Full article
(This article belongs to the Special Issue Pharmaceutically-Active Pyrazole Compounds)
Open AccessReview
Connective Tissue Growth Factor: Regulation, Diseases, and Drug Discovery
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Meishen Ren, Shanshan Yao, Tienan Chen, Hang Luo, Xiaohui Tao, Hewen Jiang, Xin Yang, Huarui Zhang, Sifan Yu, Yin Wang, Aiping Lu and Ge Zhang
Int. J. Mol. Sci. 2024, 25(9), 4692; https://doi.org/10.3390/ijms25094692 (registering DOI) - 25 Apr 2024
Abstract
In drug discovery, selecting targeted molecules is crucial as the target could directly affect drug efficacy and the treatment outcomes. As a member of the CCN family, CTGF (also known as CCN2) is an essential regulator in the progression of various diseases, including
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In drug discovery, selecting targeted molecules is crucial as the target could directly affect drug efficacy and the treatment outcomes. As a member of the CCN family, CTGF (also known as CCN2) is an essential regulator in the progression of various diseases, including fibrosis, cancer, neurological disorders, and eye diseases. Understanding the regulatory mechanisms of CTGF in different diseases may contribute to the discovery of novel drug candidates. Summarizing the CTGF-targeting and -inhibitory drugs is also beneficial for the analysis of the efficacy, applications, and limitations of these drugs in different disease models. Therefore, we reviewed the CTGF structure, the regulatory mechanisms in various diseases, and drug development in order to provide more references for future drug discovery.
Full article
(This article belongs to the Special Issue Protein–Protein Interactions: New Perspectives in Drug Discovery)
Open AccessReview
Molecular Circuits of Immune Sensing and Response to Oncolytic Virotherapy
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Darshak K. Bhatt and Toos Daemen
Int. J. Mol. Sci. 2024, 25(9), 4691; https://doi.org/10.3390/ijms25094691 (registering DOI) - 25 Apr 2024
Abstract
Oncolytic virotherapy is a promising immunotherapy approach for cancer treatment that utilizes viruses to preferentially infect and eliminate cancer cells while stimulating the immune response. In this review, we synthesize the current literature on the molecular circuits of immune sensing and response to
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Oncolytic virotherapy is a promising immunotherapy approach for cancer treatment that utilizes viruses to preferentially infect and eliminate cancer cells while stimulating the immune response. In this review, we synthesize the current literature on the molecular circuits of immune sensing and response to oncolytic virotherapy, focusing on viral DNA or RNA sensing by infected cells, cytokine and danger-associated-signal sensing by neighboring cells, and the subsequent downstream activation of immune pathways. These sequential sense-and-response mechanisms involve the triggering of molecular sensors by viruses or infected cells to activate transcription factors and related genes for a breadth of immune responses. We describe how the molecular signals induced in the tumor upon virotherapy can trigger diverse immune signaling pathways, activating both antigen-presenting-cell-based innate and T cell-based adaptive immune responses. Insights into these complex mechanisms provide valuable knowledge for enhancing oncolytic virotherapy strategies.
Full article
(This article belongs to the Special Issue Oncolytic Viruses for Cancer Immunotherapy)
Open AccessReview
Plasma Metabolite Profiling in the Search for Early-Stage Biomarkers for Lung Cancer: Some Important Breakthroughs
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Jill Meynen, Peter Adriaensens, Maarten Criel, Evelyne Louis, Karolien Vanhove, Michiel Thomeer, Liesbet Mesotten and Elien Derveaux
Int. J. Mol. Sci. 2024, 25(9), 4690; https://doi.org/10.3390/ijms25094690 (registering DOI) - 25 Apr 2024
Abstract
Lung cancer is the leading cause of cancer-related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking
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Lung cancer is the leading cause of cancer-related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking for early biomarkers to complement existing screening techniques in order to provide a safe, faster, and more accurate diagnosis. Biomarkers are biological molecules found in body fluids, such as plasma, that can be used to diagnose a condition or disease. Metabolomics has already been shown to be a powerful tool in the search for cancer biomarkers since cancer cells are characterized by impaired metabolism, resulting in an adapted plasma metabolite profile. The metabolite profile can be determined using nuclear magnetic resonance, or NMR. Although metabolomics and NMR metabolite profiling of blood plasma are still under investigation, there is already evidence for its potential for early-stage lung cancer diagnosis, therapy response, and follow-up monitoring. This review highlights some key breakthroughs in this research field, where the most significant biomarkers will be discussed in relation to their metabolic pathways and in light of the altered cancer metabolism.
Full article
(This article belongs to the Special Issue Fifty Years of Targeted Therapy in Cancer: Past, Present and Future)
Open AccessReview
Synergistic Effects of Weight Loss and Catheter Ablation: Can microRNAs Serve as Predictive Biomarkers for the Prevention of Atrial Fibrillation Recurrence?
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Carola Y. Förster, Stephan R. Künzel, Sergey Shityakov and Stavros Stavrakis
Int. J. Mol. Sci. 2024, 25(9), 4689; https://doi.org/10.3390/ijms25094689 (registering DOI) - 25 Apr 2024
Abstract
In atrial fibrillation (AF), multifactorial pathologic atrial alterations are manifested by structural and electrophysiological changes known as atrial remodeling. AF frequently develops in the context of underlying cardiac abnormalities. A critical mechanistic role played by atrial stretch is played by abnormal substrates in
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In atrial fibrillation (AF), multifactorial pathologic atrial alterations are manifested by structural and electrophysiological changes known as atrial remodeling. AF frequently develops in the context of underlying cardiac abnormalities. A critical mechanistic role played by atrial stretch is played by abnormal substrates in a number of conditions that predispose to AF, including obesity, heart failure, hypertension, and sleep apnea. The significant role of overweight and obesity in the development of AF is known; however, the differential effect of overweight, obesity, cardiovascular comorbidities, lifestyle, and other modifiable risk factors on the occurrence and recurrence of AF remains to be determined. Reverse remodeling of the atrial substrate and subsequent reduction in the AF burden by conversion into a typical sinus rhythm has been associated with weight loss through lifestyle changes or surgery. This makes it an essential pillar in the management of AF in obese patients. According to recently published research, microRNAs (miRs) may function as post-transcriptional regulators of genes involved in atrial remodeling, potentially contributing to the pathophysiology of AF. The focus of this review is on their modulation by both weight loss and catheter ablation interventions to counteract atrial remodeling in AF. Our analysis outlines the experimental and clinical evidence supporting the synergistic effects of weight loss and catheter ablation (CA) in reversing atrial electrical and structural remodeling in AF onset and in recurrent post-ablation AF by attenuating pro-thrombotic, pro-inflammatory, pro-fibrotic, arrhythmogenic, and male-sex-associated hypertrophic remodeling pathways. Furthermore, we discuss the promising role of miRs with prognostic potential as predictive biomarkers in guiding approaches to AF recurrence prevention.
Full article
(This article belongs to the Special Issue Current Research for Heart Disease Biology and Therapeutics)
Open AccessArticle
Maternal Diet High in Linoleic Acid Alters Renal Branching Morphogenesis and mTOR/AKT Signalling Genes in Rat Fetal Kidneys
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Connie McClelland, Olivia J. Holland, Nirajan Shrestha, Claire L. Jukes, Anna E. Brandon, James S. M. Cuffe, Anthony V. Perkins, Andrew J. McAinch and Deanne H. Hryciw
Int. J. Mol. Sci. 2024, 25(9), 4688; https://doi.org/10.3390/ijms25094688 (registering DOI) - 25 Apr 2024
Abstract
Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is obtained from the maternal diet during pregnancy, and is essential for normal fetal growth and development. A maternal high-LA (HLA) diet alters maternal and offspring fatty acids, maternal leptin and male/female ratio at
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Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is obtained from the maternal diet during pregnancy, and is essential for normal fetal growth and development. A maternal high-LA (HLA) diet alters maternal and offspring fatty acids, maternal leptin and male/female ratio at embryonic (E) day 20 (E20). We investigated the effects of an HLA diet on embryonic offspring renal branching morphogenesis, leptin signalling, megalin signalling and angiogenesis gene expression. Female Wistar Kyoto rats were fed low-LA (LLA; 1.44% energy from LA) or high-LA (HLA; 6.21% energy from LA) diets during pregnancy and gestation/lactation. Offspring were sacrificed and mRNA from kidneys was analysed by real-time PCR. Maternal HLA decreased the targets involved in branching morphogenesis Ret and Gdnf in offspring, independent of sex. Furthermore, downstream targets of megalin, namely mTOR, Akt3 and Prkab2, were reduced in offspring from mothers consuming an HLA diet, independent of sex. There was a trend of an increase in the branching morphogenesis target Gfra1 in females (p = 0.0517). These findings suggest that an HLA diet during pregnancy may lead to altered renal function in offspring. Future research should investigate the effects an HLA diet has on offspring kidney function in adolescence and adulthood.
Full article
(This article belongs to the Special Issue mTOR Signaling: Recent Progress)
Open AccessArticle
Identification of Quantitative Trait Loci Controlling Root Morphological Traits in an Interspecific Soybean Population Using 2D Imagery Data
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Mohammad Shafiqul Islam, Amit Ghimire, Liny Lay, Waleed Khan, Jeong-Dong Lee, Qijian Song, Hyun Jo and Yoonha Kim
Int. J. Mol. Sci. 2024, 25(9), 4687; https://doi.org/10.3390/ijms25094687 (registering DOI) - 25 Apr 2024
Abstract
Roots are the hidden and most important part of plants. They serve as stabilizers and channels for uptaking water and nutrients and play a crucial role in the growth and development of plants. Here, two-dimensional image data were used to identify quantitative trait
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Roots are the hidden and most important part of plants. They serve as stabilizers and channels for uptaking water and nutrients and play a crucial role in the growth and development of plants. Here, two-dimensional image data were used to identify quantitative trait loci (QTL) controlling root traits in an interspecific mapping population derived from a cross between wild soybean ‘PI366121’ and cultivar ‘Williams 82’. A total of 2830 single-nucleotide polymorphisms were used for genotyping, constructing genetic linkage maps, and analyzing QTLs. Forty-two QTLs were identified on twelve chromosomes, twelve of which were identified as major QTLs, with a phenotypic variation range of 36.12% to 39.11% and a logarithm of odds value range of 12.01 to 17.35. Two significant QTL regions for the average diameter, root volume, and link average diameter root traits were detected on chromosomes 3 and 13, and both wild and cultivated soybeans contributed positive alleles. Six candidate genes, Glyma.03G027500 (transketolase/glycoaldehyde transferase), Glyma.03G014500 (dehydrogenases), Glyma.13G341500 (leucine-rich repeat receptor-like protein kinase), Glyma.13G341400 (AGC kinase family protein), Glyma.13G331900 (60S ribosomal protein), and Glyma.13G333100 (aquaporin transporter) showed higher expression in root tissues based on publicly available transcriptome data. These results will help breeders improve soybean genetic components and enhance soybean root morphological traits using desirable alleles from wild soybeans.
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(This article belongs to the Special Issue Molecular Breeding and Genetic Regulation of Crops)
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Open AccessArticle
Variable Penetrance and Expressivity of a Rare Pore Loss-of-Function Mutation (p.L889V) of Nav1.5 Channels in Three Spanish Families
by
María Gallego-Delgado, Anabel Cámara-Checa, Marcos Rubio-Alarcón, David Hansoe Heredero-Jung, Laura de la Fuente-Blanco, Josu Rapún, Beatriz Plata-Izquierdo, Sara Pérez-Martín, Jorge Cebrián, Lucía Moreno de Redrojo, Belén García-Berrocal, Eva Delpón, Pedro L Sánchez, Eduardo Villacorta and Ricardo Caballero
Int. J. Mol. Sci. 2024, 25(9), 4686; https://doi.org/10.3390/ijms25094686 (registering DOI) - 25 Apr 2024
Abstract
A novel rare mutation in the pore region of Nav1.5 channels (p.L889V) has been found in three unrelated Spanish families that produces quite diverse phenotypic manifestations (Brugada syndrome, conduction disease, dilated cardiomyopathy, sinus node dysfunction, etc.) with variable penetrance among families. We clinically
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A novel rare mutation in the pore region of Nav1.5 channels (p.L889V) has been found in three unrelated Spanish families that produces quite diverse phenotypic manifestations (Brugada syndrome, conduction disease, dilated cardiomyopathy, sinus node dysfunction, etc.) with variable penetrance among families. We clinically characterized the carriers and recorded the Na+ current (INa) generated by p.L889V and native (WT) Nav1.5 channels, alone or in combination, to obtain further insight into the genotypic–phenotypic relationships in patients carrying SCN5A mutations and in the molecular determinants of the Nav1.5 channel function. The variant produced a strong dominant negative effect (DNE) since the peak INa generated by p.L889V channels expressed in Chinese hamster ovary cells, either alone (−69.4 ± 9.0 pA/pF) or in combination with WT (−62.2 ± 14.6 pA/pF), was significantly (n ≥ 17, p < 0.05) reduced compared to that generated by WT channels alone (−199.1 ± 44.1 pA/pF). The mutation shifted the voltage dependence of channel activation and inactivation to depolarized potentials, did not modify the density of the late component of INa, slightly decreased the peak window current, accelerated the recovery from fast and slow inactivation, and slowed the induction kinetics of slow inactivation, decreasing the fraction of channels entering this inactivated state. The membrane expression of p.L889V channels was low, and in silico molecular experiments demonstrated profound alterations in the disposition of the pore region of the mutated channels. Despite the mutation producing a marked DNE and reduction in the INa and being located in a critical domain of the channel, its penetrance and expressivity are quite variable among the carriers. Our results reinforce the argument that the incomplete penetrance and phenotypic variability of SCN5A loss-of-function mutations are the result of a combination of multiple factors, making it difficult to predict their expressivity in the carriers despite the combination of clinical, genetic, and functional studies.
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(This article belongs to the Special Issue Sodium Channel in Cardiovascular Diseases and Health)
Open AccessArticle
Trophic Position of the White Worm (Enchytraeus albidus) in the Context of Digestive Enzyme Genes Revealed by Transcriptomics Analysis
by
Łukasz Gajda, Agata Daszkowska-Golec and Piotr Świątek
Int. J. Mol. Sci. 2024, 25(9), 4685; https://doi.org/10.3390/ijms25094685 (registering DOI) - 25 Apr 2024
Abstract
To assess the impact of Enchytraeidae (potworms) on the functioning of the decomposer system, knowledge of the feeding preferences of enchytraeid species is required. Different food preferences can be explained by variations in enzymatic activities among different enchytraeid species, as there are no
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To assess the impact of Enchytraeidae (potworms) on the functioning of the decomposer system, knowledge of the feeding preferences of enchytraeid species is required. Different food preferences can be explained by variations in enzymatic activities among different enchytraeid species, as there are no significant differences in the morphology or anatomy of their alimentary tracts. However, it is crucial to distinguish between the contribution of microbial enzymes and the animal’s digestive capacity. Here, we computationally analyzed the endogenous digestive enzyme genes in Enchytraeus albidus. The analysis was based on RNA-Seq of COI-monohaplotype culture (PL-A strain) specimens, utilizing transcriptome profiling to determine the trophic position of the species. We also corroborated the results obtained using transcriptomics data from genetically heterogeneous freeze-tolerant strains. Our results revealed that E. albidus expresses a wide range of glycosidases, including GH9 cellulases and a specific digestive SH3b-domain-containing i-type lysozyme, previously described in the earthworm Eisenia andrei. Therefore, E. albidus combines traits of both primary decomposers (primary saprophytophages) and secondary decomposers (sapro-microphytophages/microbivores) and can be defined as an intermediate decomposer. Based on assemblies of publicly available RNA-Seq reads, we found close homologs for these cellulases and i-type lysozymes in various clitellate taxa, including Crassiclitellata and Enchytraeidae.
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(This article belongs to the Special Issue State-of-the-Art Molecular Genetics and Genomics in Poland 2.0)
Open AccessReview
The Intricacies of Renal Phosphate Reabsorption—An Overview
by
Valerie Walker
Int. J. Mol. Sci. 2024, 25(9), 4684; https://doi.org/10.3390/ijms25094684 (registering DOI) - 25 Apr 2024
Abstract
To maintain an optimal body content of phosphorus throughout postnatal life, variable phosphate absorption from food must be finely matched with urinary excretion. This amazing feat is accomplished through synchronised phosphate transport by myriads of ciliated cells lining the renal proximal tubules. These
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To maintain an optimal body content of phosphorus throughout postnatal life, variable phosphate absorption from food must be finely matched with urinary excretion. This amazing feat is accomplished through synchronised phosphate transport by myriads of ciliated cells lining the renal proximal tubules. These respond in real time to changes in phosphate and composition of the renal filtrate and to hormonal instructions. How they do this has stimulated decades of research. New analytical techniques, coupled with incredible advances in computer technology, have opened new avenues for investigation at a sub-cellular level. There has been a surge of research into different aspects of the process. These have verified long-held beliefs and are also dramatically extending our vision of the intense, integrated, intracellular activity which mediates phosphate absorption. Already, some have indicated new approaches for pharmacological intervention to regulate phosphate in common conditions, including chronic renal failure and osteoporosis, as well as rare inherited biochemical disorders. It is a rapidly evolving field. The aim here is to provide an overview of our current knowledge, to show where it is leading, and where there are uncertainties. Hopefully, this will raise questions and stimulate new ideas for further research.
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(This article belongs to the Section Molecular Biology)
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Open AccessCommunication
Apoptosis in Postmortal Tissues of Goat Spinal Cords and Survival of Resident Neural Progenitors
by
Andrey Mikhailov and Yoshiyuki Sankai
Int. J. Mol. Sci. 2024, 25(9), 4683; https://doi.org/10.3390/ijms25094683 (registering DOI) - 25 Apr 2024
Abstract
Growing demand for therapeutic tissue repair recurrently focusses scientists’ attention on critical assessment of postmortal collection of live cells, especially stem cells. Our study aimed to assess the survival of neuronal progenitors in postmortal spinal cord and their differentiation potential. Postmortal samples of
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Growing demand for therapeutic tissue repair recurrently focusses scientists’ attention on critical assessment of postmortal collection of live cells, especially stem cells. Our study aimed to assess the survival of neuronal progenitors in postmortal spinal cord and their differentiation potential. Postmortal samples of spinal cords were obtained from human-sized animals (goats) at 6, 12, 24, 36, and 54 h after slaughter. Samples were studied by immunohistology, differentiation assay, Western blot and flow cytometry for the presence and location of GD2-positive neural progenitors and their susceptibility to cell death. TUNEL staining of the goat spinal cord samples over 6–54 h postmortem revealed no difference in the number of positive cells per cross-section. Many TUNEL-positive cells were located in the gray commissure around the central canal of the spinal cord; no increase in TUNEL-positive cells was recorded in either posterior or anterior horns of the gray matter where many GD2-positive neural progenitors can be found. The active caspase 3 amount as measured by Western blot at the same intervals was moderately increasing over time. Neuronal cells were enriched by magnetic separation with antibodies against CD24; among them, the GD2-positive neural progenitor subpopulation did not overlap with apoptotic cells having high pan-caspase activity. Apoptotic cell death events are relatively rare in postmortal spinal cords and are not increased in areas of the neural progenitor cell’s location, within measured postmortal intervals, or among the CD24/GD2-positive cells. Data from our study suggest postmortal spinal cords as a valuable source for harvesting highly viable allogenic neural progenitor cells.
Full article
(This article belongs to the Special Issue Stem Cells: Physiological, Cellular and Molecular Mechanisms)
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