Journal Description
Current Issues in Molecular Biology
Current Issues in Molecular Biology
is an international, scientific, peer-reviewed, open access journal on molecular biology, published monthly online by MDPI (from Volume 43 Issue 1-2021).
- 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), PMC, PubMed, Embase, CAPlus / SciFinder, FSTA, AGRIS, and other databases.
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 16.5 days after submission; acceptance to publication is undertaken in 3.5 days (median values for papers published in this journal in the first half of 2023).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names are published annually in the journal.
Impact Factor:
3.1 (2022);
5-Year Impact Factor:
3.3 (2022)
Latest Articles
Correction: Zhang et al. Parkin, as a Regulator, Participates in Arsenic Trioxide-Triggered Mitophagy in HeLa Cells. Curr. Issues Mol. Biol. 2022, 44, 2759–2771
Curr. Issues Mol. Biol. 2023, 45(10), 7843-7844; https://doi.org/10.3390/cimb45100495 - 26 Sep 2023
Abstract
In the published publication [...]
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(This article belongs to the Special Issue Molecules at Play in Cancer)
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Open AccessEditorial
Current Issues in Molecular Biology Keep Evolving and Getting Better
Curr. Issues Mol. Biol. 2023, 45(10), 7842; https://doi.org/10.3390/cimb45100494 - 26 Sep 2023
Abstract
Current Issues in Molecular Biology (CIMB) (https://www [...]
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Open AccessArticle
T-Lymphocytes Activated by Dendritic Cells Loaded by Tumor-Derived Vesicles Decrease Viability of Melanoma Cells In Vitro
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, , , , , , and
Curr. Issues Mol. Biol. 2023, 45(10), 7827-7841; https://doi.org/10.3390/cimb45100493 - 26 Sep 2023
Abstract
Immunotherapy represents an innovative approach to cancer treatment, based on activating the body’s own immune system to combat tumor cells. Among various immunotherapy strategies, dendritic cell vaccines hold a special place due to their ability to activate T-lymphocytes, key players in cellular immunity,
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Immunotherapy represents an innovative approach to cancer treatment, based on activating the body’s own immune system to combat tumor cells. Among various immunotherapy strategies, dendritic cell vaccines hold a special place due to their ability to activate T-lymphocytes, key players in cellular immunity, and direct them to tumor cells. In this study, the influence of dendritic cells processed with tumor-derived vesicles on the viability of melanoma cells in vitro was investigated. Dendritic cells were loaded with tumor-derived vesicles, after which they were used to activate T-cells. The study demonstrated that such modified T-cells exhibit high activity against melanoma cells, leading to a decrease in their viability. Our analysis highlights the potential efficacy of this approach in developing immunotherapy against melanoma. These results provide new prospects for further research and the development of antitumor strategies based on the mechanisms of T-lymphocyte activation using tumor-derived vesicles.
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(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)
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E-Cadherin Is Expressed in Epithelial Cells of the Choroid Plexus in Human and Mouse Brains
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, , , , , , , , , and
Curr. Issues Mol. Biol. 2023, 45(10), 7813-7826; https://doi.org/10.3390/cimb45100492 - 26 Sep 2023
Abstract
Evidence showing the functional significance of the choroid plexus is accumulating. Epithelial cells with tight and adherens junctions of the choroid plexus play important roles in cerebrospinal fluid production and circadian rhythm formation. Although specific types of cadherin expressed in adherens junctions of
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Evidence showing the functional significance of the choroid plexus is accumulating. Epithelial cells with tight and adherens junctions of the choroid plexus play important roles in cerebrospinal fluid production and circadian rhythm formation. Although specific types of cadherin expressed in adherens junctions of choroid plexus epithelium (CPE) have been examined, they remained uncertain. Recent mass spectrometry and immunolocalization analysis revealed that non-epithelial cadherins, P- and N-cadherins, are expressed in the lateral membrane of CPE, whereas E-cadherin expression has not been confirmed in CPE of humans or mice. In this study, we examined E-cadherin expression in CPE of mice and humans by RT-PCR, immunohistochemical-, and Western blotting analyses. We confirmed, by using RT-PCR analysis, the mRNA expression of E-cadherin in the choroid plexus of mice. The immunohistochemical expression of E-cadherin was noted in the lateral membrane of CPE of mice and humans. We further confirmed, in Western blotting, the specific immunoreactivity for E-cadherin. Immunohistochemically, the expression of E- and N-cadherins or vimentin was unevenly distributed in some CPE, whereas that of E- and P-cadherins or β-catenin frequently co-existed in other CPE. These findings indicate that E-cadherin is expressed in the lateral membrane of CPE, possibly correlated with the expression of other cadherins and cytoplasmic proteins.
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(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning, 2nd Volume)
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Open AccessArticle
Molecular Pattern and Clinical Implications of KRAS/NRAS and BRAF Mutations in Colorectal Cancer
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, , , , , , , and
Curr. Issues Mol. Biol. 2023, 45(10), 7803-7812; https://doi.org/10.3390/cimb45100491 - 26 Sep 2023
Abstract
The aim of our study was to evaluate the incidence of KRAS/NRAS and BRAF mutations, analyze molecular patterns, and investigate associations with clinical parameters of these mutations in CRC KRAS/NRAS and BRAF mutations analyzed by next-generation sequencing. The detection rates of these mutations
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The aim of our study was to evaluate the incidence of KRAS/NRAS and BRAF mutations, analyze molecular patterns, and investigate associations with clinical parameters of these mutations in CRC KRAS/NRAS and BRAF mutations analyzed by next-generation sequencing. The detection rates of these mutations and patients’ demographics were recorded and the relationship between them was evaluated using the chi-square test. KRAS mutation was detected in 332 of 694 patients, while the mutation rates in KRAS exons 2/3 and 4 were 39.6%/3.2% and 5%, respectively. The most common mutation pattern was KRAS G12D. Five atypical variants were detected: V14I in KRAS exon 2, A18D, Q22K and T50I in exon 3, and T148P in exon 4. NRAS mutation was detected in 29 (4.5%) patients. One atypical variant L80W was detected in NRAS exon 3. BRAF mutation was seen in 37 (5.3%) patients, with BRAFV600E (83.8%) being the most common mutation pattern. NRAS mutation was significantly more frequent in patients > 64 years of age, BRAF mutation in women, and NRAS/BRAF mutations in right colon tumors. Grouping BRAF mutations into BRAFV600E and BRAFnon-V600E and their analysis according to specific tumor localizations showed that all four BRAFnon-V600E mutations originated in the rectum. In our study, KRAS exon 2 and other RAS mutation rates were higher than in the literature, while the BRAF v.600E mutation rate was similar. NRAS and BRAF mutations were significantly more frequent in the right colon. BRAF mutation was more common in women and in the right colon.
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(This article belongs to the Section Molecular Medicine)
Open AccessReview
Biomarkers in Systemic Sclerosis: An Overview
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, , , , , , , , , , , , , and
Curr. Issues Mol. Biol. 2023, 45(10), 7775-7802; https://doi.org/10.3390/cimb45100490 - 25 Sep 2023
Abstract
Systemic sclerosis (SSc) is a complex autoimmune disease characterized by significant fibrosis of the skin and internal organs, with the main involvement of the lungs, kidneys, heart, esophagus, and intestines. SSc is also characterized by macro- and microvascular damage with reduced peripheral blood
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Systemic sclerosis (SSc) is a complex autoimmune disease characterized by significant fibrosis of the skin and internal organs, with the main involvement of the lungs, kidneys, heart, esophagus, and intestines. SSc is also characterized by macro- and microvascular damage with reduced peripheral blood perfusion. Several studies have reported more than 240 pathways and numerous dysregulation proteins, giving insight into how the field of biomarkers in SSc is still extremely complex and evolving. Antinuclear antibodies (ANA) are present in more than 90% of SSc patients, and anti-centromere and anti-topoisomerase I antibodies are considered classic biomarkers with precise clinical features. Recent studies have reported that trans-forming growth factor β (TGF-β) plays a central role in the fibrotic process. In addition, interferon regulatory factor 5 (IRF5), interleukin receptor-associated kinase-1 (IRAK-1), connective tissue growth factor (CTGF), transducer and activator of transcription signal 4 (STAT4), pyrin-containing domain 1 (NLRP1), as well as genetic factors, including DRB1 alleles, are implicated in SSc damage. Several interleukins (e.g., IL-1, IL-6, IL-10, IL-17, IL-22, and IL-35) and chemokines (e.g., CCL 2, 5, 23, and CXC 9, 10, 16) are elevated in SSc. While adiponectin and maresin 1 are reduced in patients with SSc, biomarkers are important in research but will be increasingly so in the diagnosis and therapeutic approach to SSc. This review aims to present and highlight the various biomarker molecules, pathways, and receptors involved in the pathology of SSc.
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(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning, 2nd Volume)
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Open AccessReview
Therapeutic Plasma Exchange and Multiple Sclerosis Dysregulations: Focus on the Removal of Pathogenic Circulatory Factors and Altering Nerve Growth Factor and Sphingosine-1-Phosphate Plasma Levels
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and
Curr. Issues Mol. Biol. 2023, 45(10), 7749-7774; https://doi.org/10.3390/cimb45100489 - 25 Sep 2023
Abstract
Multiple sclerosis (MS) is predominantly an immune-mediated disease of the central nervous system (CNS) of unknown etiology with a possible genetic predisposition and effect of certain environmental factors. It is generally accepted that the disease begins with an autoimmune inflammatory reaction targeting oligodendrocytes
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Multiple sclerosis (MS) is predominantly an immune-mediated disease of the central nervous system (CNS) of unknown etiology with a possible genetic predisposition and effect of certain environmental factors. It is generally accepted that the disease begins with an autoimmune inflammatory reaction targeting oligodendrocytes followed by a rapid depletion of their regenerative capacity with subsequent permanent neurodegenerative changes and disability. Recent research highlights the central role of B lymphocytes and the corresponding IgG and IgM autoantibodies in newly forming MS lesions. Thus, their removal along with the modulation of certain bioactive molecules to improve neuroprotection using therapeutic plasma exchange (TPE) becomes of utmost importance. Recently, it has been proposed to determine the levels and precise effects of both beneficial and harmful components in the serum of MS patients undergoing TPE to serve as markers for appropriate TPE protocols. In this review we discuss some relevant examples, focusing on the removal of pathogenic circulating factors and altering the plasma levels of nerve growth factor and sphingosine-1-phosphate by TPE. Altered plasma levels of the reviewed molecular compounds in response to TPE reflect a successful reduction of the pro-inflammatory burden at the expense of an increase in anti-inflammatory potential in the circulatory and CNS compartments.
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(This article belongs to the Special Issue Molecular Mechanisms in Demyelinating Disorders of the Central Nervous System)
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Open AccessArticle
Defucosylated Monoclonal Antibody (H2Mab-139-mG2a-f) Exerted Antitumor Activities in Mouse Xenograft Models of Breast Cancers against Human Epidermal Growth Factor Receptor 2
Curr. Issues Mol. Biol. 2023, 45(10), 7734-7748; https://doi.org/10.3390/cimb45100488 - 23 Sep 2023
Abstract
The clinically approved human epidermal growth factor receptor 2 (HER2)-targeting monoclonal antibodies (mAbs), trastuzumab, and pertuzumab, target domains IV and II, respectively. Trastuzumab is now the standard treatment for HER2-overexpressed breast and gastric cancers, and trastuzumab in combination with pertuzumab showed clinical benefit.
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The clinically approved human epidermal growth factor receptor 2 (HER2)-targeting monoclonal antibodies (mAbs), trastuzumab, and pertuzumab, target domains IV and II, respectively. Trastuzumab is now the standard treatment for HER2-overexpressed breast and gastric cancers, and trastuzumab in combination with pertuzumab showed clinical benefit. However, there still exist patients who do not respond to the therapy. Furthermore, HER2 mutants that cannot be recognized by pertuzumab were found in tumors. Therefore, novel anti-HER2 mAbs and modalities have been desired. In our previous study, we developed a novel anti-HER2 domain I mAb, H2Mab-139 (mouse IgG1, kappa). We herein produced a defucosylated mouse IgG2a type of mAb against HER2 (H2Mab-139-mG2a-f) to enhance antibody-dependent cellular cytotoxicity (ADCC)-mediated antitumor activity. H2Mab-139-mG2a-f exhibits a high binding affinity in flow cytometry with the dissociation constant (KD) determined to be 3.9 × 10−9 M and 7.7 × 10−9 M against HER2-overexpressed Chinese hamster ovary (CHO)-K1 (CHO/HER2) and HER2-positive BT-474 cells, respectively. Moreover, we showed that H2Mab-139-mG2a-f exerted ADCC and complement-dependent cytotoxicity against CHO/HER2 and BT-474 in vitro and exhibited potent antitumor activities in mouse xenograft models. These results indicated that H2Mab-139-mG2a-f exerts antitumor effects against HER2-positive human breast cancers and is useful as an antibody treatment for HER2-positive human cancers.
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(This article belongs to the Special Issue Future Challenges of Targeted Therapy of Cancers)
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Open AccessArticle
Optimization of Plant Growth Regulators for In Vitro Mass Propagation of a Disease-Free ‘Shine Muscat’ Grapevine Cultivar
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, , , , , , , and
Curr. Issues Mol. Biol. 2023, 45(10), 7721-7733; https://doi.org/10.3390/cimb45100487 - 22 Sep 2023
Abstract
This study addresses the propagation challenges faced by ‘Shine Muscat’, a newly introduced premium grapevine cultivar in South Korea, where multiple viral infections pose considerable economic loss. The primary objective was to establish a robust in vitro propagation method for producing disease-free grapes
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This study addresses the propagation challenges faced by ‘Shine Muscat’, a newly introduced premium grapevine cultivar in South Korea, where multiple viral infections pose considerable economic loss. The primary objective was to establish a robust in vitro propagation method for producing disease-free grapes and to identify effective plant growth regulators to facilitate large-scale mass cultivation. After experimentation, 2.0 µM 6-benzyladenine (BA) exhibited superior shoot formation in the Murashige and Skoog medium compared with kinetin and thidiazuron. Conversely, α-naphthaleneacetic acid (NAA) hindered shoot growth and induced callus formation, while indole-3-butyric acid (IBA) and indole-3-acetic acid (IAA) demonstrated favorable root formation, with IBA showing better results overall. Furthermore, inter simple sequence repeat analysis confirmed the genetic stability of in vitro-cultivated seedlings using 2.0 μM BA and 1.0 μM IBA, validating the suitability of the developed propagation method for generating disease-free ‘Shine Muscat’ grapes. These findings offer promising prospects for commercial grape cultivation, ensuring a consistent supply of healthy grapes in the market.
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(This article belongs to the Special Issue Molecular Breeding and Genetics Research in Plants)
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Open AccessArticle
Targeted Delivery of Chimeric Antigen Receptor into T Cells via CRISPR-Mediated Homology-Directed Repair with a Dual-AAV6 Transduction System
Curr. Issues Mol. Biol. 2023, 45(10), 7705-7720; https://doi.org/10.3390/cimb45100486 - 22 Sep 2023
Abstract
CAR-T cell therapy involves genetically engineering T cells to recognize and attack tumour cells by adding a chimeric antigen receptor (CAR) to their surface. In this study, we have used dual transduction with AAV serotype 6 (AAV6) to integrate an anti-CD19 CAR into
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CAR-T cell therapy involves genetically engineering T cells to recognize and attack tumour cells by adding a chimeric antigen receptor (CAR) to their surface. In this study, we have used dual transduction with AAV serotype 6 (AAV6) to integrate an anti-CD19 CAR into human T cells at a known genomic location. The first viral vector expresses the Cas9 endonuclease and a guide RNA (gRNA) targeting the T cell receptor alpha constant locus, while the second vector carries the DNA template for homology-mediated CAR insertion. We evaluated three gRNA candidates and determined their efficiency in generating indels. The AAV6 successfully delivered the CRISPR/Cas9 machinery in vitro, and molecular analysis of the dual transduction showed the integration of the CAR transgene into the desired location. In contrast to the random integration methods typically used to generate CAR-T cells, targeted integration into a known genomic locus can potentially lower the risk of insertional mutagenesis and provide more stable levels of CAR expression. Critically, this method also results in the knockout of the endogenous T cell receptor, allowing target cells to be derived from allogeneic donors. This raises the exciting possibility of “off-the-shelf” universal immunotherapies that would greatly simplify the production and administration of CAR-T cells.
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(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)
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Open AccessReview
An Overview of Systemic Targeted Therapy in Renal Cell Carcinoma, with a Focus on Metastatic Renal Cell Carcinoma and Brain Metastases
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, , , , , , and
Curr. Issues Mol. Biol. 2023, 45(9), 7680-7704; https://doi.org/10.3390/cimb45090485 - 21 Sep 2023
Abstract
The most commonly diagnosed malignancy of the urinary system is represented by renal cell carcinoma. Various subvariants of RCC were described, with a clear-cell type prevailing in about 85% of all RCC tumors. Patients with metastases from renal cell carcinoma did not have
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The most commonly diagnosed malignancy of the urinary system is represented by renal cell carcinoma. Various subvariants of RCC were described, with a clear-cell type prevailing in about 85% of all RCC tumors. Patients with metastases from renal cell carcinoma did not have many effective therapies until the end of the 1980s, as long as hormonal therapy and chemotherapy were the only options available. The outcomes were unsatisfactory due to the poor effectiveness of the available therapeutic options, but then interferon-alpha and interleukin-2 showed treatment effectiveness, providing benefits but only for less than half of the patients. However, it was not until 2004 that targeted therapies emerged, prolonging the survival rate. Currently, new technologies and strategies are being developed to improve the actual efficacy of available treatments and their prognostic aspects. This article summarizes the mechanisms of action, importance, benefits, adverse events of special interest, and efficacy of immunotherapy in metastatic renal cell carcinoma, with a focus on brain metastases.
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(This article belongs to the Special Issue Future Challenges of Targeted Therapy of Cancers)
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Open AccessArticle
Unraveling the Potential of Isorhamnetin as an Adjuvant in Depression Treatment with Escitalopram
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Curr. Issues Mol. Biol. 2023, 45(9), 7668-7679; https://doi.org/10.3390/cimb45090484 - 21 Sep 2023
Abstract
Oxidative stress and inflammation are implicated in depression. While selective serotonin reuptake inhibitors (SSRIs) like escitalopram are commonly prescribed as first-line treatments, their inconsistent efficacy and delayed onset of action necessitates the exploration of adjunctive therapies. Isorhamnetin, a flavonol, has shown antioxidant and
[...] Read more.
Oxidative stress and inflammation are implicated in depression. While selective serotonin reuptake inhibitors (SSRIs) like escitalopram are commonly prescribed as first-line treatments, their inconsistent efficacy and delayed onset of action necessitates the exploration of adjunctive therapies. Isorhamnetin, a flavonol, has shown antioxidant and anti-inflammatory properties that makes exploring its antidepressant effect attractive. This study aims to investigate the adjuvant potential of isorhamnetin in combination with escitalopram to enhance its antidepressant efficacy in a lipopolysaccharide (LPS)-induced depression model using Swiss albino mice. Behavioral paradigms, such as the forced swim test and open field test, were employed to assess depressive symptoms, locomotion, and sedation. Additionally, enzyme-linked immunosorbent assays were utilized to measure Nrf2, BDNF, HO-1, NO, and IL-6 levels in the prefrontal cortex and hippocampus. The results demonstrate that isorhamnetin significantly improves the antidepressant response of escitalopram, as evidenced by reduced floating time in the forced swim test. Moreover, isorhamnetin enhanced antidepressant effects of escitalopram and effectively restored depleted levels of Nrf2, BDNF, and HO-1 in the cortex caused by LPS-induced depression. Isorhamnetin shows promise in enhancing the efficacy of conventional antidepressant therapy through antioxidant and anti-inflammatory effects.
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(This article belongs to the Topic Neuroprotection by Drugs, Nutraceuticals and Physical Activity, 2nd Volume)
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Open AccessArticle
6-Hydroxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline Alleviates Oxidative Stress and NF-κB-Mediated Inflammation in Rats with Experimental Parkinson’s Disease
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, , , and
Curr. Issues Mol. Biol. 2023, 45(9), 7653-7667; https://doi.org/10.3390/cimb45090483 - 21 Sep 2023
Abstract
A study was conducted to investigate the effects of different doses of 6-hydroxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (HTHQ) on motor coordination scores, brain tissue morphology, the expression of tyrosine hydroxylase, the severity of oxidative stress parameters, the levels of the p65 subunit of nuclear factor kappa-light-chain-enhancer of
[...] Read more.
A study was conducted to investigate the effects of different doses of 6-hydroxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (HTHQ) on motor coordination scores, brain tissue morphology, the expression of tyrosine hydroxylase, the severity of oxidative stress parameters, the levels of the p65 subunit of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) factor, and the inflammatory response in rats during the development of rotenone-induced Parkinsonism. The findings indicate that HTHQ, with its antioxidant attributes, reduced the levels of 8-isoprostane, lipid oxidation products, and protein oxidation products. The decrease in oxidative stress due to HTHQ led to a reduction in the mRNA content of proinflammatory cytokines and myeloperoxidase activity, accompanying the drop in the expression of the factor NF-κB. These alterations promoted an improvement in motor coordination scores and increased tyrosine hydroxylase levels, whereas histopathological changes in the brain tissue of the experimental animals were attenuated. HTHQ exhibited greater effectiveness than the comparative drug rasagiline based on the majority of variables.
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(This article belongs to the Special Issue Molecular Mechanism and Regulation in Neuroinflammation)
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Open AccessEditorial
New Sight: Enzymes as Targets for Drug Development
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Curr. Issues Mol. Biol. 2023, 45(9), 7650-7652; https://doi.org/10.3390/cimb45090482 - 20 Sep 2023
Abstract
In the dynamic realm of medical research, a resounding chord is struck by recent studies that have propelled drug discovery to new horizons across a spectrum of disciplines [...]
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(This article belongs to the Special Issue New Sight: Enzymes as Targets for Drug Development)
Open AccessCase Report
Safety and Efficacy of Neoadjuvant Chemoimmunotherapy in Gastric Cancer Patients with a PD-L1 Positive Status: A Case Report
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, , , and
Curr. Issues Mol. Biol. 2023, 45(9), 7642-7649; https://doi.org/10.3390/cimb45090481 - 19 Sep 2023
Abstract
Introduction: The landscape of gastric cancer treatment has changed owing to the widespread use of immune checkpoint inhibitors. Autophagy, involved in regulating the immune system, is a potential trigger of immunity in tumors. This study aims to find molecular-based evidence for the effectiveness
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Introduction: The landscape of gastric cancer treatment has changed owing to the widespread use of immune checkpoint inhibitors. Autophagy, involved in regulating the immune system, is a potential trigger of immunity in tumors. This study aims to find molecular-based evidence for the effectiveness of FLOT chemotherapy with immune checkpoint inhibitors in gastric cancer patients. Materials and Methods: Three patients with advanced gastric cancer received FLOT neoadjuvant chemotherapy with immunotherapy and surgery. IHC was used to determine the PD-L1 status. Real-time PCR was used to analyze expression patterns of transcriptional growth factors, AKT/mTOR signaling components, PD-1, PD-L1, PD-L2 and LC3B. The LC3B content was measured via Western blotting analysis. Results: The combination of FLOT neoadjuvant chemotherapy and immunotherapy was found to be efficient in patients with a PD-L1-positive status. Gastric tumors with a PD-L1-positive status exhibited autophagy activation and decreased PD-1 expression. Conclusions: FLOT chemotherapy combined with immune checkpoint inhibitors showed high efficacy in gastric cancer patients with a positive PD-L1 status. Autophagy was involved in activating the tumor immunity. Further research is needed to clarify the mechanism of effective anticancer treatment.
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(This article belongs to the Special Issue Molecular-Based Approaches in Therapy for Gastrointestinal Cancers, 2nd Edition)
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Open AccessArticle
p62 Is a Potential Biomarker for Risk of Malignant Transformation of Oral Potentially Malignant Disorders (OPMDs)
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, , , , , , , , and
Curr. Issues Mol. Biol. 2023, 45(9), 7630-7641; https://doi.org/10.3390/cimb45090480 - 19 Sep 2023
Abstract
To determine the intracellular behavior of p62, a marker of selective autophagy, in oral potentially malignant disorders (OPMDs). This retrospective study includes 70 patients who underwent biopsy or surgical resection and were definitively diagnosed with OPMDs. Immunohistochemical staining for p62, XPO1, p53, and
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To determine the intracellular behavior of p62, a marker of selective autophagy, in oral potentially malignant disorders (OPMDs). This retrospective study includes 70 patients who underwent biopsy or surgical resection and were definitively diagnosed with OPMDs. Immunohistochemical staining for p62, XPO1, p53, and ki67 was performed on all samples and positive cell occupancy was calculated. We statistically investigated the correlation between protein expression in OPMDs and the association between malignant transformation, clinicopathological characteristics, and occupancy. ki67 expression was negatively correlated with p62 expression in the nucleus (p < 0.01) and positively correlated with p62 expression in the cytoplasm (p < 0.01). For malignant transformation, the expression of p62 in the nucleus (p = 0.03) was significantly lower in malignant transformation cases, whereas the expression of p62 in the cytoplasm (p = 0.03) and the aggregation expression (p < 0.01) were significantly higher. Our results suggest that the function of p62 is altered by its subcellular localization. In addition, defects in selective autophagy occur in cases of malignant transformation, suggesting that p62 is a potential biomarker of the risk of malignant transformation of OPMDs.
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(This article belongs to the Special Issue Oral Cancer: Prophylaxis, Etiopathogenesis and Treatment)
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Open AccessArticle
Effect of the Aqueous Extract of Chrysobalanus icaco Leaves on Maternal Reproductive Outcomes and Fetal Development in Wistar Rats
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Curr. Issues Mol. Biol. 2023, 45(9), 7617-7629; https://doi.org/10.3390/cimb45090479 - 19 Sep 2023
Abstract
Toxicological studies on medicinal plants are essential to ensure their safety and effectiveness in treating various diseases. Despite the species Chrysobalanus icaco L. being popularly used in the treatment of several diseases due to the pharmacological properties of its bioactive compounds, there are
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Toxicological studies on medicinal plants are essential to ensure their safety and effectiveness in treating various diseases. Despite the species Chrysobalanus icaco L. being popularly used in the treatment of several diseases due to the pharmacological properties of its bioactive compounds, there are few studies in the literature regarding its toxicity regarding reproduction. Therefore, the purpose of this study was to assess the potential embryotoxic and teratogenic effects of the aqueous extract of C. icaco leaves (AECi) on Wistar rats. Animals were given AECi at doses of 100, 200, and 400 mg/kg during the pre-implantation and organogenesis periods. Data were analyzed using ANOVA followed by Tukey’s test and Kruskal–Wallis. Pregnant rats treated during the pre-implantation period showed no signs of reproductive toxicity. Rats that received AECi at 100, 200, and 400 mg/kg during organogenesis did not exhibit any signs of maternal systemic toxicity or significant differences in gestational and embryotoxic parameters. Some skeletal changes were observed in the treated groups. Therefore, it can be suggested that AECi at doses of 100, 200, and 400 mg/kg is safe for treated animals and does not induce reproductive toxicity under the experimental conditions applied, but it also caused low systemic toxicity.
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(This article belongs to the Topic Safety and Toxicological Risks of Medicinal Plants and Natural Products: Mechanistic Insights)
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Open AccessReview
Interactions between the DNA Damage Response and the Telomere Complex in Carcinogenesis: A Hypothesis
Curr. Issues Mol. Biol. 2023, 45(9), 7582-7616; https://doi.org/10.3390/cimb45090478 - 19 Sep 2023
Abstract
Contrary to what was once thought, direct cancer originating from normal stem cells seems to be extremely rare. This is consistent with a preneoplastic period of telomere length reduction/damage in committed cells that becomes stabilized in transformation. Multiple observations suggest that telomere damage
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Contrary to what was once thought, direct cancer originating from normal stem cells seems to be extremely rare. This is consistent with a preneoplastic period of telomere length reduction/damage in committed cells that becomes stabilized in transformation. Multiple observations suggest that telomere damage is an obligatory step preceding its stabilization. During tissue turnover, the telomeres of cells undergoing differentiation can be damaged as a consequence of defective DNA repair caused by endogenous or exogenous agents. This may result in the emergence of new mechanism of telomere maintenance which is the final outcome of DNA damage and the initial signal that triggers malignant transformation. Instead, transformation of stem cells is directly induced by primary derangement of telomere maintenance mechanisms. The newly modified telomere complex may promote survival of cancer stem cells, independently of telomere maintenance. An inherent resistance of stem cells to transformation may be linked to specific, robust mechanisms that help maintain telomere integrity.
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(This article belongs to the Special Issue Targeting Tumor Microenvironment for Cancer Therapy, 2nd Edition)
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Open AccessArticle
Colorectal Cancer Archaeome: A Metagenomic Exploration, Tunisia
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, , , , , , , and
Curr. Issues Mol. Biol. 2023, 45(9), 7572-7581; https://doi.org/10.3390/cimb45090477 - 19 Sep 2023
Abstract
Colorectal cancer (CRC) is a serious public health problem known to have a multifactorial etiology. The association between gut microbiota and CRC has been widely studied; however, the link between archaea and CRC has not been sufficiently studied. To investigate the involvement of
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Colorectal cancer (CRC) is a serious public health problem known to have a multifactorial etiology. The association between gut microbiota and CRC has been widely studied; however, the link between archaea and CRC has not been sufficiently studied. To investigate the involvement of archaea in colorectal carcinogenesis, we performed a metagenomic analysis of 68 formalin-embedded paraffin fixed tissues from tumoral (n = 33) and healthy mucosa (n = 35) collected from 35 CRC Tunisian patients. We used two DNA extraction methods: Generead DNA FFPE kit (Qiagen, Germantown, MD, USA) and Chelex. We then sequenced the samples using Illumina Miseq. Interestingly, DNA extraction exclusively using Chelex generated enough DNA for sequencing of all samples. After data filtering and processing, we reported the presence of archaeal sequences, which represented 0.33% of all the reads generated. In terms of abundance, we highlighted a depletion in methanogens and an enrichment in Halobacteria in the tumor tissues, while the correlation analysis revealed a significant association between the Halobacteria and the tumor mucosa (p < 0.05). We reported a strong correlation between Natrialba magadii, Sulfolobus acidocaldarius, and tumor tissues, and a weak correlation between Methanococcus voltae and healthy adjacent mucosa. Here, we demonstrated the feasibility of archaeome analysis from formol fixed paraffin-embedded (FFPE) tissues using simple protocols ranging from sampling to data analysis, and reported a significant association between Halobacteria and tumor tissues in Tunisian patients with CRC. The importance of our study is that it represents the first metagenomic analysis of Tunisian CRC patients’ gut microbiome, which consists of sequencing DNA extracted from paired tumor-adjacent FFPE tissues collected from CRC patients. The detection of archaeal sequences in our samples confirms the feasibility of carrying out an archaeome analysis from FFPE tissues using a simple DNA extraction protocol. Our analysis revealed the enrichment of Halobacteria, especially Natrialba magadii, in tumor mucosa compared to the normal mucosa in CRC Tunisian patients. Other species were also associated with CRC, including Sulfolobus acidocaldarius and Methanococcus voltae, which is a methanogenic archaea; both species were found to be correlated with adjacent healthy tissues.
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(This article belongs to the Special Issue Molecular-Based Approaches in Therapy for Gastrointestinal Cancers)
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Pathophysiological Implications of Interstitial Cajal-like Cells (ICC-like) in Uterus: A Comparative Study with Gastrointestinal ICCs
Curr. Issues Mol. Biol. 2023, 45(9), 7557-7571; https://doi.org/10.3390/cimb45090476 - 15 Sep 2023
Abstract
The main function of interstitial cells of Cajal (ICCs) is to regulate gastrointestinal peristalsis by acting as a “pacemaker” cell by generating spontaneous slow electrical waves. In 2005, electron microscopy revealed a cell type similar to ICCs (ICC-like) outside the gastrointestinal tract, with
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The main function of interstitial cells of Cajal (ICCs) is to regulate gastrointestinal peristalsis by acting as a “pacemaker” cell by generating spontaneous slow electrical waves. In 2005, electron microscopy revealed a cell type similar to ICCs (ICC-like) outside the gastrointestinal tract, with contractile activity and c-Kit+ immunohistochemistry shared with ICCs. Among the locations where ICC-like cells have been observed, it is in the uterus where they have a significant functional and pathophysiological role. These cells are involved in obstetric phenomena of contractile action, such as ascending sperm transport, embryo implantation, pregnancy, delivery, and the expulsion of menstrual debris. Within the pathophysiology related to these cells, we find obstetric alterations such as recurrent miscarriages, premature deliveries, abolition of uterine contractions, and failures of embryo implantation, in addition to other common conditions in the fertile age, such as endometriosis and leiomyoma.
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(This article belongs to the Collection Feature Papers in Current Issues in Molecular Biology)
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