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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 February 2025 | Viewed by 15013

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Dr. Luis Felipe Jiménez-García

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Guest Editor

Facultad de Ciencias, Universidad Nacional Autónoma de México, Mexico City, Mexico
Interests: microbes; ultrastructure; cell biology

Special Issue Information

Dear Colleagues,

The “Cell and Molecular Biology” Special Issue in IJMS welcomes original research, reviews, and short communication papers covering a broad range of topics that include:

Emerging single-cell analysis technologies;
Epigenetic modifications;
Non-coding RNA molecules;
Cellular metabolism in disease;
Novel therapeutic targets;
CRISPR gene editing;
Stem cells in regenerative medicine;
Microbiome influence;
Cancer biology;
Immunology;
Cell structure and ultrastructure.

Various interdisciplinary approaches such as genomics, proteomics, bioinformatics, and functional genomics are also highlighted. The aim of this Special Issue is to provide an opportunity for researchers to exchange ideas, promote collaboration, and share the latest scientific discoveries in this dynamic and exciting field of Cell and Molecular Biology. Innovative methods and cutting-edge technologies are welcomed, and the published works will contribute to the scientific community, leading to future progress and advancements in the field.

Dr. Luis Felipe Jiménez-García
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Gene expression
Cellular signaling
Computational biology
Molecular mechanisms
Signal transduction
Epigenetics
Proteomics
Transcriptomics
DNA repair
Stem cells
Apoptosis
Cancer biology
Synthetic biology
Drug discovery
Molecular imaging
Genome engineering
CRISPR/Cas9
Immunology
Neurobiology
Metabolism
RNA Biology

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Published Papers (8 papers)

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Research

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23 pages, 7668 KiB

Open AccessArticle

Impact of Reduced Saliva Production on Intestinal Integrity and Microbiome Alterations: A Sialoadenectomy Mouse Model Study

by Kanna Maita, Hisako Fujihara, Mitsuki Matsumura, Moeko Miyakawa, Ryoko Baba, Hiroyuki Morimoto, Ryoko Nakayama, Yumi Ito, Koji Kawaguchi and Yoshiki Hamada

Int. J. Mol. Sci. 2024, 25(22), 12455; https://doi.org/10.3390/ijms252212455 - 20 Nov 2024

Viewed by 827

Abstract

This study investigates the effect of reduced saliva production on intestinal histological structure and microbiome composition using a sialoadenectomy murine model, evaluating differences in saliva secretion, body weight, intestinal histopathological changes, and microbiome alteration using 16S rRNA gene sequencing across three groups (control, sham, and sialoadenectomy). For statistical analysis, one-way analysis of variance and multiple comparisons using Bonferroni correction were performed. p-values < 0.05 were considered statistically significant. Microbiome analysis was performed using Qiime software. The results show that reduced saliva secretion leads to structural changes in the intestinal tract, including shorter and atrophic villi, deformed Paneth cells, decreased goblet cell density, and immunohistochemical changes in epidermal growth factor and poly(ADP-ribose) polymerase-1, especially at three months after surgery. They also showed significant alterations in the intestinal microbiome, including increased Lactobacillaceae and altered populations of Ruminococcaceae and Peptostreptococcaceae, suggesting potential inflammatory responses and decreased short-chain fatty acid production. However, by 12 months after surgery, these effects appeared to be normalized, indicating potential compensatory mechanisms. Interestingly, sham-operated mice displayed favorable profiles, possibly due to immune activation from minor surgical intervention. This study underscores saliva’s essential role in intestinal condition, emphasizing the “oral–gut axis” and highlighting broader implications for the relationship between oral and systemic health. Full article

(This article belongs to the Special Issue Recent Research on Cell and Molecular Biology)

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18 pages, 18326 KiB

Open AccessArticle

Combined Analysis of Metabolomics and Transcriptome Revealed the Effect of Bacillus thuringiensis on the 5th Instar Larvae of Dendrolimus kikuchii Matsumura

by Jinyan Li, Qiang Guo, Bin Yang and Jielong Zhou

Int. J. Mol. Sci. 2024, 25(21), 11823; https://doi.org/10.3390/ijms252111823 - 4 Nov 2024

Cited by 1 | Viewed by 805

Abstract

Dendrolimus kikuchii Matsumura (D. kikuchii) is a serious pest of coniferous trees. Bacillus thuringiensis (Bt) has been widely studied and applied as a biological control agent for a variety of pests. Here, we found that the mortality rate of D. kikuchii larvae after being fed Bt reached 95.33% at 24 h; the midgut membrane tissue was ulcerated and liquefied, the MDA content in the midgut tissue decreased and the SOD, CAT and GPx enzyme activities increased, indicating that Bt has toxic effects on D. kikuchii larvae. In addition, transmission electron microscopy showed that Bt infection caused severe deformation of the nucleus of the midgut tissue of D. kikuchii larvae, vacuoles in the nucleolus, swelling and shedding of microvilli, severe degradation of mitochondria and endoplasmic reticulum and decreased number. Surprisingly, metabolomics and transcriptome association analysis revealed that four metabolic-related signaling pathways, Nicotinate and nicotinamide metabolism, Longevity regulating pathway—worm, Vitamin digestion and absorption and Lysine degradation, were co-annotated in larvae. More surprisingly, Niacinamide was a common differential metabolite in the first three signaling pathways, and both Niacinamide and L-2-Aminoadipic acid were reduced. The differentially expressed genes involved in the four signaling pathways, including NNT, ALDH, PNLIP, SETMAR, GST and RNASEK, were significantly down-regulated, but only SLC23A1 gene expression was up-regulated. Our results illustrate the effects of Bt on the 5th instar larvae of D. kikuchii at the tissue, cell and molecular levels, and provide theoretical support for the study of Bt as a new biological control agent for D. kikuchii. Full article

(This article belongs to the Special Issue Recent Research on Cell and Molecular Biology)

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25 pages, 7412 KiB

Open AccessArticle

Proteomic Analysis of Rap1A GTPase Signaling-Deficient C57BL/6 Mouse Pancreas and Functional Studies Identify an Essential Role of Rap1A in Pancreas Physiology

by Durrey Shahwar, Sadaf Baqai, Faisal Khan, M. Israr Khan, Shafaq Javaid, Abdul Hameed, Aisha Raza, Sadaf Saleem Uddin, Hina Hazrat, M. Hafizur Rahman, Syed Ghulam Musharraf and Maqsood A. Chotani

Int. J. Mol. Sci. 2024, 25(15), 8013; https://doi.org/10.3390/ijms25158013 - 23 Jul 2024

Viewed by 1681

Abstract

Ras-related Rap1A GTPase is implicated in pancreas β-cell insulin secretion and is stimulated by the cAMP sensor Epac2, a guanine exchange factor and activator of Rap1 GTPase. In this study, we examined the differential proteomic profiles of pancreata from C57BL/6 Rap1A-deficient (Null) and control wild-type (WT) mice with nanoLC-ESI-MS/MS to assess targets of Rap1A potentially involved in insulin regulation. We identified 77 overlapping identifier proteins in both groups, with 8 distinct identifier proteins in Null versus 56 distinct identifier proteins in WT mice pancreata. Functional enrichment analysis showed four of the eight Null unique proteins, ERO1-like protein β (Ero1lβ), triosephosphate isomerase (TP1), 14-3-3 protein γ, and kallikrein-1, were exclusively involved in insulin biogenesis, with roles in insulin metabolism. Specifically, the mRNA expression of Ero1lβ and TP1 was significantly (p < 0.05) increased in Null versus WT pancreata. Rap1A deficiency significantly affected glucose tolerance during the first 15–30 min of glucose challenge but showed no impact on insulin sensitivity. Ex vivo glucose-stimulated insulin secretion (GSIS) studies on isolated Null islets showed significantly impaired GSIS. Furthermore, in GSIS-impaired islets, the cAMP-Epac2-Rap1A pathway was significantly compromised compared to the WT. Altogether, these studies underscore an essential role of Rap1A GTPase in pancreas physiological function. Full article

(This article belongs to the Special Issue Recent Research on Cell and Molecular Biology)

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17 pages, 5944 KiB

Open AccessArticle

Effects of Chronic Exposure to Low Doses of Rotenone on Dopaminergic and Cholinergic Neurons in the CNS of Hemigrapsus sanguineus

by Elena Kotsyuba and Vyacheslav Dyachuk

Int. J. Mol. Sci. 2024, 25(13), 7159; https://doi.org/10.3390/ijms25137159 - 28 Jun 2024

Viewed by 1009

Abstract

Rotenone, as a common pesticide and insecticide frequently found in environmental samples, may be present in aquatic habitats worldwide. Exposure to low concentrations of this compound may cause alterations in the nervous system, thus contributing to Parkinsonian motor symptoms in both vertebrates and invertebrates. However, the effects of chronic exposure to low doses of rotenone on the activity of neurotransmitters that govern motor functions and on the specific molecular mechanisms leading to movement morbidity remain largely unknown for many aquatic invertebrates. In this study, we analyzed the effects that rotenone poisoning exerts on the activity of dopamine (DA) and acetylcholine (ACh) synthesis enzymes in the central nervous system (CNS) of Asian shore crab, Hemigrapsus sanguineus (de Haan, 1835), and elucidated the association of its locomotor behavior with Parkinson’s-like symptoms. An immunocytochemistry analysis showed a reduction in tyrosine hydroxylase (TH) in the median brain and the ventral nerve cord (VNC), which correlated with the subsequent decrease in the locomotor activity of shore crabs. We also observed a variation in cholinergic neurons’ activity, mostly in the ventral regions of the VNC. Moreover, the rotenone-treated crabs showed signs of damage to ChAT-lir neurons in the VNC. These data suggest that chronic treatment with low doses of rotenone decreases the DA level in the VNC and the ACh level in the brain and leads to progressive and irreversible reductions in the crab’s locomotor activity, life span, and changes in behavior. Full article

(This article belongs to the Special Issue Recent Research on Cell and Molecular Biology)

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19 pages, 20639 KiB

Open AccessArticle

Microscopic Analysis of Nuclear Speckles in a Viviparous Reptile

by Jeniffer Acosta-Cárdenas, Luis Felipe Jiménez-García, Sarai de Jesús Cruz-Gómez, Ana Paulina Mendoza-von der Borch and María de Lourdes Segura-Valdez

Int. J. Mol. Sci. 2024, 25(10), 5281; https://doi.org/10.3390/ijms25105281 - 12 May 2024

Viewed by 1622

Abstract

Nuclear speckles are compartments enriched in splicing factors present in the nucleoplasm of eucaryote cells. Speckles have been studied in mammalian culture and tissue cells, as well as in some non-mammalian vertebrate cells and invertebrate oocytes. In mammals, their morphology is linked to the transcriptional and splicing activities of the cell through a recruitment mechanism. In rats, speckle morphology depends on the hormonal cycle. In the present work, we explore whether a similar situation is also present in non-mammalian cells during the reproductive cycle. We studied the speckled pattern in several tissues of a viviparous reptile, the lizard Sceloporus torquatus, during two different stages of reproduction. We used immunofluorescence staining against splicing factors in hepatocytes and oviduct epithelium cells and fluorescence and confocal microscopy, as well as ultrastructural immunolocalization and EDTA contrast in Transmission Electron Microscopy. The distribution of splicing factors in the nucleoplasm of oviductal cells and hepatocytes coincides with the nuclear-speckled pattern described in mammals. Ultrastructurally, those cell types display Interchromatin Granule Clusters and Perichromatin Fibers. In addition, the morphology of speckles varies in oviduct cells at the two stages of the reproductive cycle analyzed, paralleling the phenomenon observed in the rat. The results show that the morphology of speckles in reptile cells depends upon the reproductive stage as it occurs in mammals. Full article

(This article belongs to the Special Issue Recent Research on Cell and Molecular Biology)

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30 pages, 7308 KiB

Open AccessArticle

Effects of S-Adenosylhomocysteine Hydrolase Downregulation on Wnt Signaling Pathway in SW480 Cells

by Ivana Pavičić, Filip Rokić and Oliver Vugrek

Int. J. Mol. Sci. 2023, 24(22), 16102; https://doi.org/10.3390/ijms242216102 - 8 Nov 2023

Cited by 1 | Viewed by 2378

Abstract

S-adenosylhomocysteine hydrolase (AHCY) deficiency results mainly in hypermethioninemia, developmental delay, and is potentially fatal. In order to shed new light on molecular aspects of AHCY deficiency, in particular any changes at transcriptome level, we enabled knockdown of AHCY expression in the colon cancer cell line SW480 to simulate the environment occurring in AHCY deficient individuals. The SW480 cell line is well known for elevated AHCY expression, and thereby represents a suitable model system, in particular as AHCY expression is regulated by MYC, which, on the other hand, is involved in Wnt signaling and the regulation of Wnt-related genes, such as the β-catenin co-transcription factor LEF1 (lymphoid enhancer-binding factor 1). We selected LEF1 as a potential target to investigate its association with S-adenosylhomocysteine hydrolase deficiency. This decision was prompted by our analysis of RNA-Seq data, which revealed significant changes in the expression of genes related to the Wnt signaling pathway and genes involved in processes responsible for epithelial-mesenchymal transition (EMT) and cell proliferation. Notably, LEF1 emerged as a common factor in these processes, showing increased expression both on mRNA and protein levels. Additionally, we show alterations in interconnected signaling pathways linked to LEF1, causing gene expression changes with broad effects on cell cycle regulation, tumor microenvironment, and implications to cell invasion and metastasis. In summary, we provide a new link between AHCY deficiency and LEF1 serving as a mediator of changes to the Wnt signaling pathway, thereby indicating potential connections of AHCY expression and cancer cell phenotype, as Wnt signaling is frequently associated with cancer development, including colorectal cancer (CRC). Full article

(This article belongs to the Special Issue Recent Research on Cell and Molecular Biology)

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14 pages, 4313 KiB

Open AccessArticle

Tyrosine Kinase Inhibitor Profiling Using Multiple Forskolin-Responsive Reporter Cells

by Yamato Kasahara, Sakura Tamamura, Gen Hiyama, Motoki Takagi, Kazuya Nakamichi, Yuta Doi, Kentaro Semba, Shinya Watanabe and Kosuke Ishikawa

Int. J. Mol. Sci. 2023, 24(18), 13863; https://doi.org/10.3390/ijms241813863 - 8 Sep 2023

Viewed by 2073

Abstract

We have developed a highly sensitive promoter trap vector system using transposons to generate reporter cells with high efficiency. Using an EGFP/luciferase reporter cell clone responsive to forskolin, which is thought to activate adenylate cyclase, isolated from human chronic myelogenous leukemia cell line K562, we found several compounds unexpectedly caused reporter responses. These included tyrosine kinase inhibitors such as dasatinib and cerdulatinib, which were seemingly unrelated to the forskolin-reactive pathway. To investigate whether any other clones of forskolin-responsive cells would show the same response, nine additional forskolin-responsive clones, each with a unique integration site, were generated and quantitatively evaluated by luciferase assay. The results showed that each clone represented different response patterns to the reactive compounds. Also, it became clear that each of the reactive compounds could be profiled as a unique pattern by the 10 reporter clones. When other TKIs, mainly bcr-abl inhibitors, were evaluated using a more focused set of five reporter clones, they also showed unique profiling. Among them, dasatinib and bosutinib, and imatinib and bafetinib showed homologous profiling. The tyrosine kinase inhibitors mentioned above are approved as anticancer agents, and the system could be used for similarity evaluation, efficacy prediction, etc., in the development of new anticancer agents. Full article

(This article belongs to the Special Issue Recent Research on Cell and Molecular Biology)

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Review

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18 pages, 1314 KiB

Open AccessReview

Molecular Basis of Hydatidiform Moles—A Systematic Review

by Shadha Nasser Mohammed Bahutair, Rajani Dube, Manjunatha Goud Bellary Kuruba, Rasha Aziz Attia Salama, Mohamed Anas Mohamed Faruk Patni, Subhranshu Sekhar Kar and Rakhee Kar

Int. J. Mol. Sci. 2024, 25(16), 8739; https://doi.org/10.3390/ijms25168739 - 10 Aug 2024

Viewed by 2070

Abstract

Gestational trophoblastic diseases (GTDs) encompass a spectrum of conditions characterized by abnormal trophoblastic cell growth, ranging from benign molar pregnancies to malignant trophoblastic neoplasms. This systematic review explores the molecular underpinnings of GTDs, focusing on genetic and epigenetic factors that influence disease progression and clinical outcomes. Based on 71 studies identified through systematic search and selection criteria, key findings include dysregulations in tumor suppressor genes such as p53, aberrant apoptotic pathways involving BCL-2 (B-cell lymphoma), and altered expression of growth factor receptors and microRNAs (micro-ribose nucleic acid). These molecular alterations not only differentiate molar pregnancies from normal placental development but also contribute to their clinical behavior, from benign moles to potentially malignant forms. The review synthesizes insights from immunohistochemical studies and molecular analyses to provide a comprehensive understanding of GTD pathogenesis and implications for personalized care strategies. Full article

(This article belongs to the Special Issue Recent Research on Cell and Molecular Biology)

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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

1. Identification LCK as master regulator of TNBC neutrophils enrichment and polarization: in silico reanalysis with extensive systems biology approach

2. TNBC cells effect on neutrophils survival, migration and polarization. An In vitro study using cell lines and healthy neutrophils cocultured with TNBC Vs Luminal Cell lines

3. Tyrosine Kinase Inhibitor Profiling Using Multiple XXXX-responsive Reporter Cells"

4. Identification of XXXX upregulated by stressors that stimulate ATF4"

5. Microscopic analysis of nuclear speckles in the vivíparous lizard Sceloporus torquatus-Guest Editor

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