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 16.8 days after submission; acceptance to publication is undertaken in 2.7 days (median values for papers published in this journal in the first half of 2024).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names are published annually in the journal.
Impact Factor:
2.8 (2023);
5-Year Impact Factor:
2.9 (2023)
Latest Articles
Improvement of Quality and Disease Resistance for a Heavy-Panicle Hybrid Restorer Line, R600, in Rice (Oryza sativa L.) by Gene Pyramiding Breeding
Curr. Issues Mol. Biol. 2024, 46(10), 10762-10778; https://doi.org/10.3390/cimb46100639 (registering DOI) - 25 Sep 2024
Abstract
The utilization of heavy-panicle hybrid rice exemplifies the successful integration of architectural enhancement and heterosis, which has been widely adopted in the southwest rice-producing area of China. Iterative improvement in disease resistance and grain quality of heavy-panicle hybrid rice varieties is crucial to
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The utilization of heavy-panicle hybrid rice exemplifies the successful integration of architectural enhancement and heterosis, which has been widely adopted in the southwest rice-producing area of China. Iterative improvement in disease resistance and grain quality of heavy-panicle hybrid rice varieties is crucial to promote their sustainable utilization. Here, we performed a molecular design breeding strategy to introgress beneficial alleles of broad-spectrum disease resistance and grain quality into a heavy-panicle hybrid backbone restorer line Shuhui 600 (R600). We successfully developed introgression lines through marker-assisted selection to pyramid major genes (Wxb + ALKA-GC + Pigm + Xa23) derived from three parents (Huanghuazhan, I135, I488), which significantly enhance grain quality and confer resistance to rice blast and bacterial blight (BB). The improved parental R600 line (iR600) exhibited superior grain quality and elevated disease resistance while maintaining the heavy-panicle architecture and high-yield capacity of R600. Moreover, the iR600 was crossed with male sterility line 608A to obtain a new heavy-panicle hybrid rice variety with excellent eating and cooking quality (ECQ) and high yield potential. This study presents an effective breeding strategy for rice breeders to expedite the improvement of grain quality and disease resistance in heavy-panicle hybrid rice.
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(This article belongs to the Section Molecular Plant Sciences)
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TRIM25, TRIM28 and TRIM59 and Their Protein Partners in Cancer Signaling Crosstalk: Potential Novel Therapeutic Targets for Cancer
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De Chen Chiang and Beow Keat Yap
Curr. Issues Mol. Biol. 2024, 46(10), 10745-10761; https://doi.org/10.3390/cimb46100638 (registering DOI) - 25 Sep 2024
Abstract
Aberrant expression of TRIM proteins has been correlated with poor prognosis and metastasis in many cancers, with many TRIM proteins acting as key oncogenic factors. TRIM proteins are actively involved in many cancer signaling pathways, such as p53, Akt, NF-κB, MAPK, TGFβ, JAK/STAT,
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Aberrant expression of TRIM proteins has been correlated with poor prognosis and metastasis in many cancers, with many TRIM proteins acting as key oncogenic factors. TRIM proteins are actively involved in many cancer signaling pathways, such as p53, Akt, NF-κB, MAPK, TGFβ, JAK/STAT, AMPK and Wnt/β-catenin. Therefore, this review attempts to summarize how three of the most studied TRIMs in recent years (i.e., TRIM25, TRIM28 and TRIM59) are involved directly and indirectly in the crosstalk between the signaling pathways. A brief overview of the key signaling pathways involved and their general cross talking is discussed. In addition, the direct interacting protein partners of these TRIM proteins are also highlighted in this review to give a picture of the potential protein–protein interaction that can be targeted for future discovery and for the development of novel therapeutics against cancer. This includes some examples of protein partners which have been proposed to be master switches to various cancer signaling pathways.
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(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Honokiol Is More Potent than Magnolol in Reducing Head and Neck Cancer Cell Growth
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Robert Kleszcz, Dawid Dorna, Maciej Stawny and Jarosław Paluszczak
Curr. Issues Mol. Biol. 2024, 46(10), 10731-10744; https://doi.org/10.3390/cimb46100637 (registering DOI) - 25 Sep 2024
Abstract
The efficacy of treatment of head and neck squamous cell carcinoma (HNSCC) patients is still unsatisfactory, and there is an ongoing search for novel therapies. Locoregionally advanced HNSCC cases, which frequently require combined surgery and chemoradiotherapy, are especially difficult to treat. Natural compounds,
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The efficacy of treatment of head and neck squamous cell carcinoma (HNSCC) patients is still unsatisfactory, and there is an ongoing search for novel therapies. Locoregionally advanced HNSCC cases, which frequently require combined surgery and chemoradiotherapy, are especially difficult to treat. Natural compounds, like Magnolia-derived lignans—honokiol (HON) and magnolol (MAG)—can reduce cancer cell growth but retain a good safety profile and thus may show benefit as adjuvant therapeutics. The aim of this study was to evaluate the anti-cancer effects of HON and MAG in HNSCC cell lines and compare their effects between cisplatin-sensitive and cisplatin-tolerant cells. Cell viability was evaluated in FaDu and SCC-040 cells growing as monolayers and as spheroids. The effect of HON and MAG on the cell cycle, apoptosis, and gene expression was compared between wild-type FaDu cells and cisplatin persister FaDu cells. We observed that HON and MAG were more potent in reducing cell viability in cisplatin persister FaDu cells, although this effect was not directly followed by increased rates of apoptosis. Thus, HON’s and MAG’s capacity to affect cisplatin persister cells needs further studies. In general, we observed that HON exerted stronger cytotoxic effects than MAG in HNSCC cells, and the difference in their anti-cancer activity was especially pronounced in cells cultured in 3D.
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(This article belongs to the Special Issue Phytochemicals in Cancer Chemoprevention and Treatment)
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The Enhancement of Regulatory T Cell Maturation and Th1/Th2 Balance through FOXP3 Expression by Lactobacillus paracasei in an Ovalbumin-Induced Allergic Skin Animal Model
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Chin-Feng Liu, Wen-Yu Chao, Tsung-Wei Shih, Chun-Lin Lee and Tzu-Ming Pan
Curr. Issues Mol. Biol. 2024, 46(10), 10714-10730; https://doi.org/10.3390/cimb46100636 (registering DOI) - 24 Sep 2024
Abstract
Chronic allergic skin conditions, including atopic dermatitis (AD), are characterized by pruritus, erythema, xerosis, desquamation, and inflammation, significantly impacting quality of life. Long-term steroid use, while common in treatment, carries the risk of adverse effects. Previous studies have demonstrated the potential of Lactobacillus
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Chronic allergic skin conditions, including atopic dermatitis (AD), are characterized by pruritus, erythema, xerosis, desquamation, and inflammation, significantly impacting quality of life. Long-term steroid use, while common in treatment, carries the risk of adverse effects. Previous studies have demonstrated the potential of Lactobacillus paracasei subsp. paracasei NTU 101 (NTU 101) in alleviating AD symptoms from a preventive perspective. This study, however, focuses on exploring NTU 101’s therapeutic potential by investigating its effects on regulatory T cell (Treg) maturation and Th1/Th2 balance. The results revealed that NTU 101 administration effectively reduced serum IgE levels and inflammatory cell infiltration in the skin, leading to a significant improvement in both epidermal and dermal thickness in the AD model. Additionally, NTU 101 modulated the immune response by increasing the proportion of CD4+/IL-4+ (Th2) cells in the spleen and concurrently enhancing FOXP3 expression in CD4+/CD25+ cells, which is critical for Treg cell development. This immune modulation was further associated with a rebalancing of the Th1/Th2 ratio, achieved by increasing the proportion of CD4+/IFN-γ+ (Th1) cells. Moreover, NTU 101 influenced the proportion of CD4+IL-17+ (Th17) cells, thereby supporting neutrophil maturation and promoting allergen clearance, ultimately mitigating AD symptoms. These findings underscore the potential of NTU 101 not only in managing AD symptoms but also in modulating key immune pathways involved in the pathogenesis of the disease, offering a promising alternative or adjunct to conventional steroid therapies.
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(This article belongs to the Special Issue Natural Product in Skin Inflammation and Barrier Function Damage)
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Open AccessArticle
Genetics of 21-OH Deficiency and Genotype–Phenotype Correlation: Experience of the Hellenic National Referral Center
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Irene Fylaktou, Anny Mertzanian, Ioanna Farakla, Alexandros Gryparis, Ioannis Anargyros Vasilakis, Maria Binou, Evangelia Charmandari, Christina Kanaka-Gantenbein and Amalia Sertedaki
Curr. Issues Mol. Biol. 2024, 46(10), 10696-10713; https://doi.org/10.3390/cimb46100635 (registering DOI) - 24 Sep 2024
Abstract
21-hydroxylase deficiency (21-OHD) represents the most common form of congenital adrenal hyperplasia (CAH) due to CYP21A2 gene pathogenic variants. Τhe aim of this study was the identification of CYP21A2 variants in 500 subjects of Greek origin with a suspicion of 21-OHD and, by
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21-hydroxylase deficiency (21-OHD) represents the most common form of congenital adrenal hyperplasia (CAH) due to CYP21A2 gene pathogenic variants. Τhe aim of this study was the identification of CYP21A2 variants in 500 subjects of Greek origin with a suspicion of 21-OHD and, by using the existing hormonal assessment and genotypes of the 500 subjects tested, to identify a biomarker that could differentiate between the heterozygotes and the cases with no pathogenic variants identified. Five hundred subjects with clinical suspicion of 21-OHD underwent CYP21A2 gene sequencing and Multiplex Ligation Dependent Probe Amplification (MLPA). Genetic diagnosis was achieved in 27.4% of the subjects tested, most of which presented with the non-classic form (NC) of 21-OHD. Heterozygotes accounted for 42.6% of cases, whereas no pathogenic variants were identified in 27% of cases. De novo aberrations, duplications, and five novel variants were also identified. Statistical analysis revealed that the difference between the basal and 60′ post-ACTH stimulation 17-hydroxyprogesterone concentrations (Δ17-OHP60-0) could be a potential biomarker (p < 0.05) distinguishing the heterozygotes from the cases with no pathogenic variants identified, although no clear cut-off value could be set. Further analysis revealed overlapping clinical manifestations among all the subjects tested. The presented phenotypic traits of the subjects tested and the inability to identify a discriminative biochemical marker highlight the importance of comprehensive CYP21A2 genotyping to ascertain the correct genetic diagnosis and proper genetic counselling.
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(This article belongs to the Special Issue Genomic Analysis of Common Disease)
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Enhancing Crop Resilience: Insights from Labdane-Related Diterpenoid Phytoalexin Research in Rice (Oryza sativa L.)
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Shiquan Bian, Zhong Li, Shaojie Song, Xiao Zhang, Jintao Shang, Wanli Wang, Dewen Zhang and Dahu Ni
Curr. Issues Mol. Biol. 2024, 46(9), 10677-10695; https://doi.org/10.3390/cimb46090634 (registering DOI) - 23 Sep 2024
Abstract
Rice (Oryza sativa L.), as one of the most significant food crops worldwide, holds paramount importance for global food security. Throughout its extensive evolutionary journey, rice has evolved a diverse array of defense mechanisms to fend off pest and disease infestations. Notably,
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Rice (Oryza sativa L.), as one of the most significant food crops worldwide, holds paramount importance for global food security. Throughout its extensive evolutionary journey, rice has evolved a diverse array of defense mechanisms to fend off pest and disease infestations. Notably, labdane-related diterpenoid phytoalexins play a crucial role in aiding rice in its response to both biotic and abiotic stresses. This article provides a comprehensive review of the research advancements pertaining to the chemical structures, biological activities, and biosynthetic pathways, as well as the molecular regulatory mechanisms, underlying labdane-related diterpenoid phytoalexins discovered in rice. This insight into the molecular regulation of labdane-related diterpenoid phytoalexin biosynthesis offers valuable perspectives for future research aimed at improving crop resilience and productivity.
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(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2024)
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Biosynthesis and Extraction of Chlorophyll, Carotenoids, Anthocyanins, and Betalaine In Vivo and In Vitro
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Xinxin Yu, Hao Wang, Xingchun Xiang, Jingjing Fu, Xin Wang, Yuanhang Zhou and Wang Xing
Curr. Issues Mol. Biol. 2024, 46(9), 10662-10676; https://doi.org/10.3390/cimb46090633 (registering DOI) - 23 Sep 2024
Abstract
As natural bioactive compounds, plant pigments play crucial roles not only in plant phenotype, growth, development, and adaptation to stress but also hold unique value in biotechnology, healthcare, and industrial applications. There is growing interest in the biosynthesis and acquisition of plant pigments.
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As natural bioactive compounds, plant pigments play crucial roles not only in plant phenotype, growth, development, and adaptation to stress but also hold unique value in biotechnology, healthcare, and industrial applications. There is growing interest in the biosynthesis and acquisition of plant pigments. Thus, this paper explores emerging extraction methods of natural pigments and elucidates the biosynthesis pathways of four key plant pigments, chlorophylls, carotenoids, anthocyanins, and betalaine in vivo and in vitro. We comprehensively discuss the application of solvent, supercritical fluid [extraction], ultrasonic, and microwave-assisted extraction techniques, as well as introducing key enzymes, precursors, and synthetic pathways involved in pigment synthesis. δ-Aminolevulinic acid represents a pivotal initiating enzyme for chlorophyll synthesis, whereas isopentenylpyrophosphate, (IPP) and dimethylallyl pyrophosphate, (DMAPP) are closely associated with carotenoid biosynthesis. Phenylalanine and tyrosine are critical substances for anthocyanin and betalaine synthesis, respectively. Hence, crucial genes such as chlI, crtB, PGT8, CYP76AD1, and BvDODA can be employed for heterologous biosynthesis in vitro to meet the demand for increased plant pigment amount. As a pivotal determinant of plant coloration, an in-depth exploration into the high-quality acquisition of plant pigments can provide a basis for developing superior pigments and offer new insights into increasing pigment yield.
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(This article belongs to the Section Molecular Plant Sciences)
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The Role of Biomarkers in the Early Diagnosis of Gastric Cancer: A Study on CCR5, CCL5, PDGF, and EphA7
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Süleyman Bademler, Berkay Kılıç, Muhammed Üçüncü, Alisan Zirtiloglu and Burak İlhan
Curr. Issues Mol. Biol. 2024, 46(9), 10651-10661; https://doi.org/10.3390/cimb46090632 (registering DOI) - 23 Sep 2024
Abstract
Despite the use of screening programs, gastric cancer (GC) diagnosis may only be possible at an advanced stage. In this study, we examined the serum levels of C-C chemokine receptor type 5 (CCR5), C-C motif chemokine ligand 5 (CCL5), platelet-derived growth factor (PDGF),
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Despite the use of screening programs, gastric cancer (GC) diagnosis may only be possible at an advanced stage. In this study, we examined the serum levels of C-C chemokine receptor type 5 (CCR5), C-C motif chemokine ligand 5 (CCL5), platelet-derived growth factor (PDGF), and EphrinA7 (EphA7) in patients with gastric carcinoma and healthy controls to investigate the significance and usability of these potential biomarkers in the early diagnosis of GC. The study enrolled 69 GC patients and 40 healthy individuals. CCR5, CCL5, PDGF-BB, and EphA7 levels, which have been identified in the carcinogenesis of many cancers, were measured in the blood samples using the ELISA method. CCR5, CCL5, PDGF-BB, and EphA7 were all correlated with GC diagnosis (CCR5, p < 0.001, r = −0.449; CCL5, p = 0.014, r = −0.234; PDGF-BB, p < 0.001, r = −0.700; EPHA7, p < 0.001, r = −0.617). The serum CCR5, EphA7, and especially the PDGF-BB levels of the patients diagnosed with GC were discovered to be significantly higher compared to the healthy controls. PDGF-BB had the highest positive and negative predictive values when evaluated in ROC analysis to determine its diagnostic significance (cut-off value: 59.8 ng/L; AUC: 0.92 (0.87–0.97)). As far as we know, this is the first study to investigate the potential connection between GC and these four biomarkers. The fact that serum CCR5, CCL5, EphA7, and especially PDGF-BB levels in the patient group were significantly higher compared to healthy controls indicates that they can be used with high accuracy in the early diagnosis of GC. In addition, the levels of CCR5, PDGF-BB, and EphA7 can be used as important indicators to predict the biological behavior and prognosis of GC.
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(This article belongs to the Section Molecular Medicine)
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Marine Bioactive Molecules as Inhibitors of the Janus Kinases: A Comparative Molecular Docking and Molecular Dynamics Simulation Approach
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Emad A. Ahmed and Salah A. Abdelsalam
Curr. Issues Mol. Biol. 2024, 46(9), 10635-10650; https://doi.org/10.3390/cimb46090631 (registering DOI) - 23 Sep 2024
Abstract
A treasure trove of naturally occurring biomolecules can be obtained from sea living organisms to be used as potential antioxidant and anti-inflammatory agents. These bioactive molecules can target signaling molecules involved in the severity of chronic autoimmune diseases such as rheumatoid arthritis (RA).
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A treasure trove of naturally occurring biomolecules can be obtained from sea living organisms to be used as potential antioxidant and anti-inflammatory agents. These bioactive molecules can target signaling molecules involved in the severity of chronic autoimmune diseases such as rheumatoid arthritis (RA). The intracellular tyrosine kinases family, Janus kinases (JAKs, includes JAK1, JAK2, and JAK3), is implicated in the pathogenesis of RA through regulating several cytokines and inflammatory processes. In the present study, we conducted molecular docking and structural analysis investigations to explore the role of a set of bioactive molecules from marine sources that can be used as JAKs’ specific inhibitors. Around 200 antioxidants and anti-inflammatory molecules out of thousands of marine molecules found at the Comprehensive Marine Natural Products Database (CMNPD) website, were used in that analysis. The details of the interacting residues were compared to the recent FDA approved inhibitors tofacitinib and baricitinib for data validation. The shortlisted critical amino acids residues of our pharmacophore-based virtual screening were LYS905, GLU957, LEU959, and ASP1003 at JAK1, GLU930 and LEU932 at JAK2, and GLU905 and CYS909 of JAK3. Interestingly, marine biomolecules such as Sargachromanol G, Isopseudopterosin E, Seco-Pseudopterosin, and CID 10071610 showed specific binding and significantly higher binding energy to JAK1 active/potential sites when being compared with the approved inhibitors. In addition, Zoanthoxanthin and Fuscoside E bind to JAK2′s critical residues, GLU930 and LEU932. Moreover, Phorbaketal and Fuscoside E appear to be potential candidates that can inhibit JAK3 activity. These results were validated using molecular dynamics simulation for the docked complexes, JAK1(6sm8)/SG, JAK2 (3jy9)/ZAX, and JAK3 (6pjc)/Fuscoside E, where stable and lower binding energy were found based on analyzing set of parameters, discussed below (videos are attached). A promising role of these marine bioactive molecules can be confirmed in prospective preclinical/clinical investigations using rheumatoid arthritis models.
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(This article belongs to the Special Issue Synthesis and Theoretical Study of Bioactive Molecules)
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Open AccessCorrection
Correction: Chao et al. MicroRNA-22-3p and MicroRNA-149-5p Inhibit Human Hepatocellular Carcinoma Cell Growth and Metastasis Properties by Regulating Methylenetetrahydrofolate Reductase. Curr. Issues Mol. Biol. 2022, 44, 952–962
by
Chao Li, Xiang Li, Han Wang, Xihan Guo, Jinglun Xue, Xu Wang and Juan Ni
Curr. Issues Mol. Biol. 2024, 46(9), 10633-10634; https://doi.org/10.3390/cimb46090630 (registering DOI) - 23 Sep 2024
Abstract
Author Correction: We apologize for unintentionally using the wrong figures (Figure 5b and Figure 6e) in the original article [...]
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(This article belongs to the Topic Clinical, Translational and Basic Research on Liver Diseases)
Open AccessArticle
Establishment of an Agrobacterium tumefaciens-Mediated Transformation System for Hirsutella sinensis
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Lijuan Wu, Xinkun Hu, Shen Yan, Zenglin Wu, Xuzhong Tang, Lei Xie, Yujie Qiu, Rui Li, Ji Chen and Mengliang Tian
Curr. Issues Mol. Biol. 2024, 46(9), 10618-10632; https://doi.org/10.3390/cimb46090629 (registering DOI) - 22 Sep 2024
Abstract
Ophiocordyceps sinensis (Berk.) is a complex is formed by Hepialidae larvae and Hirsutella sinensis. Infestation by H. sinensis, interaction with host larvae, and fruiting body development are three crucial processes affecting the formation of O. sinensis. However, research on the
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Ophiocordyceps sinensis (Berk.) is a complex is formed by Hepialidae larvae and Hirsutella sinensis. Infestation by H. sinensis, interaction with host larvae, and fruiting body development are three crucial processes affecting the formation of O. sinensis. However, research on the molecular mechanism of O. sinensis formation has been hindered by the lack of effective genetic transformation protocols. Therefore, Agrobacterium tumefaciens-mediated transformation (ATMT) was adopted to genetically transform two H. sinensis strains and optimize the transformation conditions. The results revealed that the most suitable Agrobacterium strain for H. sinensis transformation was AGL1, and that the surfactant Triton X-100 could also induce ATMT, although less effectively than acetosyringone (AS). In addition, the endogenous promoters of H. sinensis genes had a stronger ability to drive the expression of the target gene than did the exogenous promoter. The optimal transformation conditions were as follows: AS and hygromycin B concentrations of 100 μM and 50 μg/mL, respectively; A. tumefaciens OD600 of 0.4; cocultivation at 18 °C for 24 h; and H. sinensis used within three passages. The results lay a foundation for the functional study of key regulatory genes involved in the formation of O. sinensis.
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(This article belongs to the Section Molecular Microbiology)
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Development of Yein-Early, a Unique Fruit-Color and Leaf-Shape Mutant of Citrus unshiu, and Its Specific Selection Marker
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Jung-Gwon Ko, Chang-Ho Eun and In-Jung Kim
Curr. Issues Mol. Biol. 2024, 46(9), 10606-10617; https://doi.org/10.3390/cimb46090628 (registering DOI) - 21 Sep 2024
Abstract
Citrus unshiu Marc. cv. Miyagawa-wase is one of the most widely cultivated citrus varieties on Jeju Island in Republic of Korea. Mutation breeding is a useful tool for inducing genetic diversity by causing genomic mutations in a short period of time. We previously
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Citrus unshiu Marc. cv. Miyagawa-wase is one of the most widely cultivated citrus varieties on Jeju Island in Republic of Korea. Mutation breeding is a useful tool for inducing genetic diversity by causing genomic mutations in a short period of time. We previously conducted mutation breeding using gamma irradiation to develop new varieties of C. unshiu. Here, we describe one of these varieties, Yein-early, which has a redder peel, greater hardness, and higher sugar content compared with the wild type (WT). Yein-early leaves also showed a unique phenotype compared with the WT, characterized by longer longitudinal length, shorter transverse length, stronger curling, and longer petiole length. Genome resequencing of Yein-early and the WT uncovered significant single-nucleotide polymorphisms (SNPs) and insertions/deletions (InDels). These variations were crucial in identifying molecular markers unique to Yein-early. In addition, we developed an allele-specific PCR marker specifically targeting a homozygous SNP in Yein-early that distinguishes it from the WT and other citrus varieties. This study contributes to the understanding of pigment synthesis in fruits and provides a valuable tool for selection of the novel Yein-early variety in citrus breeding programs.
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(This article belongs to the Special Issue Advances in Multi-Omics for Functional Genomics Studies and Molecular Breeding)
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Using NGS to Uncover the Corruption of a Peptide Phage Display Selection
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Danna Kamstrup Sell, Babak Bakhshinejad, Anders Wilgaard Sinkjaer, Ida Melissa Dawoodi, Mette Neiegaard Wiinholt, Ane Beth Sloth, Camilla Stavnsbjerg and Andreas Kjaer
Curr. Issues Mol. Biol. 2024, 46(9), 10590-10605; https://doi.org/10.3390/cimb46090627 (registering DOI) - 21 Sep 2024
Abstract
Phage display has been widely used to identify peptides binding to a variety of biological targets. In the current work, we planned to select novel peptides targeting CD4 through screening of a commercial phage display library (New England Biolabs Ph.D.TM-7). After
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Phage display has been widely used to identify peptides binding to a variety of biological targets. In the current work, we planned to select novel peptides targeting CD4 through screening of a commercial phage display library (New England Biolabs Ph.D.TM-7). After three rounds of biopanning, 57 phage clones were Sanger-sequenced. These clones represented 30 unique peptide sequences, which were subjected to phage ELISA, resulting in the identification of two potential target binders. Following peptide synthesis, downstream characterization was conducted using fluorescence plate-based assay, flow cytometry, SPR, and confocal microscopy. The results revealed that neither of the peptides identified in the Sanger-based phage display selection exhibited specific binding toward CD4. The naïve library and the phage pool recovered from the third round of biopanning were then subjected to next-generation sequencing (NGS). The results of NGS indicated corruption of the selection output by a phage already known as a fast-propagating clone whose target-unrelated enrichment can shed light on the misidentification of target-binding peptides through phage display. This work provides an in-depth insight into some of the challenges encountered in peptide phage display selection. Furthermore, our data highlight that NGS, by exploring a broader sequence space and providing a more precise picture of the composition of biopanning output, can be used to refine the selection protocol and avoid misleading the process of ligand identification. We hope that these findings can describe some of the complexities of phage display selection and offer help to fellow researchers who have faced similar situations.
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(This article belongs to the Special Issue Technological Advances around Next-Generation Sequencing Application)
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The Potential of CRISPR/Cas9 to Circumvent the Risk Factor Neurotoxin β-N-oxalyl-L-α, β-diaminopropionic acid Limiting Wide Acceptance of the Underutilized Grass Pea (Lathyrus sativus L.)
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Abreham Bekele-Alemu, Deribew Girma-Tola and Ayalew Ligaba-Osena
Curr. Issues Mol. Biol. 2024, 46(9), 10570-10589; https://doi.org/10.3390/cimb46090626 (registering DOI) - 21 Sep 2024
Abstract
Grass pea (Lathyrus sativus L.) is a protein-rich crop that is resilient to various abiotic stresses, including drought. However, it is not cultivated widely for human consumption due to the neurotoxin β-N-oxalyl-L-α, β-diaminopropionic acid (β-ODAP) and its association with neurolathyrism.
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Grass pea (Lathyrus sativus L.) is a protein-rich crop that is resilient to various abiotic stresses, including drought. However, it is not cultivated widely for human consumption due to the neurotoxin β-N-oxalyl-L-α, β-diaminopropionic acid (β-ODAP) and its association with neurolathyrism. Though some varieties with low β-ODAP have been developed through classical breeding, the β-ODAP content is increasing due to genotype x environment interactions. This review covers grass pea nutritional quality, β-ODAP biosynthesis, mechanism of paralysis, traditional ways to reduce β-ODAP, candidate genes for boosting sulfur-containing amino acids, and the potential and targets of gene editing to reduce β-ODAP content. Recently, two key enzymes (β-ODAP synthase and β-cyanoalanine synthase) have been identified in the biosynthetic pathway of β-ODAP. We proposed four strategies through which the genes encoding these enzymes can be targeted and suppressed using CRISPR/Cas9 gene editing. Compared to its homology in Medicago truncatula, the grass pea β-ODAP synthase gene sequence and β-cyanoalanine synthase showed 62.9% and 95% similarity, respectively. The β-ODAP synthase converts the final intermediate L-DAPA into toxic β-ODAP, whist β-cyanoalanine synthase converts O-Acetylserine into β-isoxazolin-5-on-2-yl-alanine. Since grass pea is low in methionine and cysteine amino acids, improvement of these amino acids is also needed to boost its protein content. This review contains useful resources for grass pea improvement while also offering potential gene editing strategies to lower β-ODAP levels.
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(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Effects of Curcumin on Radiation/Chemotherapy-Induced Oral Mucositis: Combined Meta-Analysis, Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation
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Zhi-Xing Chen, Ya-Shi Qin, Bang-Hui Shi, Bi-Yun Gao, Ren-Chuan Tao and Xiang-Zhi Yong
Curr. Issues Mol. Biol. 2024, 46(9), 10545-10569; https://doi.org/10.3390/cimb46090625 - 20 Sep 2024
Abstract
The study aims to investigate the effects of curcumin on radiation/chemotherapy-induced oral mucositis (R/CIOM) and preliminarily explore its mechanism. Randomized controlled trials were identified from the PubMed, Embase, Web of Science, Cochrane Library, Medline, and Google Scholar databases. RevMan 5.4 was used for
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The study aims to investigate the effects of curcumin on radiation/chemotherapy-induced oral mucositis (R/CIOM) and preliminarily explore its mechanism. Randomized controlled trials were identified from the PubMed, Embase, Web of Science, Cochrane Library, Medline, and Google Scholar databases. RevMan 5.4 was used for statistical analysis to calculate the combined risk ratios (RRs). The mechanism was analyzed through network pharmacology, molecular docking, and a molecular dynamics simulation. The targets of curcumin were collected in HERB, PharmMapper, Targetnet, Swiss Target Prediction, and SuperPred. OMIM, GeneCards, and Disgenet were used to collect relevant targets for R/CIOM. Cytoscape software 3.8.0 was used to construct the component-target-pathway network. Protein–Protein Interaction (PPI) networks were constructed using the STRING database. GO and KEGG enrichment analyses were performed by Metascape. AutoDock Vina 4.2 software was used for molecular docking. The molecular dynamics simulation was performed by Gromacs v2022.03. It is found that 12 studies involving 565 patients were included. Meta-analyses showed that curcumin reduced the incidence of severe R/CIOM (RR 0.42 [0.24, 0.75]) and the mean severity of R/CIOM (MD -0.93 [−1.34, −0.52]). Eleven core target genes were identified in the treatment of R/CIOM with curcumin. The results of molecular docking and the molecular dynamics simulation showed that curcumin had strong binding energy and stability with target proteins including MAPK3, SRC, and TNF. Overall, these findings suggest curcumin can effectively improve severe R/CIOM, perhaps by affecting MAPK3, SRC, and TNF.
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(This article belongs to the Special Issue The Role of Bioactives in Inflammation)
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Open AccessArticle
Intranasal Insulin Eases Autism in Rats via GDF-15 and Anti-Inflammatory Pathways
by
Duygu Burcu Arda, Kerem Can Tunç, Mehmet Fatih Bozkurt, Ejder Saylav Bora, Ayşe Çiğel and Oytun Erbaş
Curr. Issues Mol. Biol. 2024, 46(9), 10530-10544; https://doi.org/10.3390/cimb46090624 - 20 Sep 2024
Abstract
In rat models, it is well-documented that chronic administration of propionic acid (PPA) leads to autism-like behaviors. Although the intranasal (IN) insulin approach is predominantly recognized for its effects on food restriction, it has also been shown to enhance cognitive memory by influencing
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In rat models, it is well-documented that chronic administration of propionic acid (PPA) leads to autism-like behaviors. Although the intranasal (IN) insulin approach is predominantly recognized for its effects on food restriction, it has also been shown to enhance cognitive memory by influencing various proteins, modulating anti-inflammatory pathways in the brain, and reducing signaling molecules such as interleukins. This study seeks to explore the potential therapeutic benefits of IN insulin in a rat model of autism induced by PPA. Thirty male Wistar albino rats were categorized into three cohorts: the control group, the PPA-induced autism (250 mg/kg/day intraperitoneal PPA dosage for five days) group, treated with saline via IN, and the PPA-induced autism group, treated with 25 U/kg/day (250 µL/kg/day) insulin via IN. All treatments were administered for 15 days. After behavioral testing, all animals were euthanized, and brain tissue and blood samples were collected for histopathological and biochemical assessments. Following insulin administration, a substantial reduction in autism symptoms was observed in all three social behavior tests conducted on the rats. Moreover, insulin exhibited noteworthy capabilities in decreasing brain MDA, IL-2, IL-17, and TNF-α levels within autism models. Additionally, there is a notable elevation in the brain nerve growth factor level (p < 0.05) and GDF-15 (p < 0.05). The assessment of cell counts within the hippocampal region and cerebellum revealed that insulin displayed effects in decreasing glial cells and inducing a significant augmentation in cell types such as the Purkinje and Pyramidal cells. The administration of insulin via IN exhibits alleviating effects on autism-like behavioral, biochemical, and histopathological alterations induced by PPA in rats. Insulin-dependent protective effects show anti-inflammatory, anti-oxidative, and neuroprotective roles of insulin admitted nasally.
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(This article belongs to the Topic Autism: Molecular Bases, Diagnosis and Therapies, 2nd Volume)
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Open AccessArticle
Antidiabetic and Antihyperlipidemic Activities and Molecular Mechanisms of Phyllanthus emblica L. Extract in Mice on a High-Fat Diet
by
Hsing-Yi Lin, Cheng-Hsiu Lin, Yueh-Hsiung Kuo and Chun-Ching Shih
Curr. Issues Mol. Biol. 2024, 46(9), 10492-10529; https://doi.org/10.3390/cimb46090623 - 20 Sep 2024
Abstract
We planned to explore the protective activities of extract of Phyllanthus emblica L. (EPE) on insulin resistance and metabolic disorders including hyperlipidemia, visceral obesity, and renal dysfunction in high-fat diet (HFD)-progressed T2DM mice. Mice treatments included 7 weeks of HFD induction followed by
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We planned to explore the protective activities of extract of Phyllanthus emblica L. (EPE) on insulin resistance and metabolic disorders including hyperlipidemia, visceral obesity, and renal dysfunction in high-fat diet (HFD)-progressed T2DM mice. Mice treatments included 7 weeks of HFD induction followed by EPE, fenofibrate (Feno), or metformin (Metf) treatment daily for another 4-week HFD in HFD-fed mice. Finally, we harvested blood to analyze some tests on circulating glycemia and blood lipid levels. Western blotting analysis was performed on target gene expressions in peripheral tissues. The present findings indicated that EPE treatment reversed the HFD-induced increases in blood glucose, glycosylated HbA1C, and insulin levels. Our findings proved that treatment with EPE in HFD mice effectively controls hyperglycemia and hyperinsulinemia. Our results showed that EPE reduced blood lipid levels, including a reduction in blood triglyceride (TG), total cholesterol (TC), and free fatty acid (FFA); moreover, EPE reduced blood leptin levels and enhanced adiponectin concentrations. EPE treatment in HFD mice reduced BUN and creatinine in both blood and urine and lowered albumin levels in urine; moreover, EPE decreased circulating concentrations of inflammatory NLR family pyrin domain containing 3 (NLRP3) and kidney injury molecule-1 (KIM-1). These results indicated that EPE displayed antihyperglycemic and antihyperlipidemic activities but alleviated renal dysfunction in HFD mice. The histology examinations indicated that EPE treatment decreased adipose hypertrophy and hepatic ballooning, thus contributing to amelioration of lipid accumulation. EPE treatment decreased visceral fat amounts and led to improved systemic insulin resistance. For target gene expression levels, EPE enhanced AMP-activated protein kinase (AMPK) phosphorylation expressions both in livers and skeletal muscles and elevated the muscular membrane glucose transporter 4 (GLUT4) expressions. Treatment with EPE reduced hepatic glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) expressions to suppress glucose production in the livers and decreased phosphorylation of glycogen synthase kinase 3β (GSK3β) expressions to affect hepatic glycogen synthesis, thus convergently contributing to an antidiabetic effect and improving insulin resistance. The mechanism of the antihyperlipidemic activity of EPE involved a decrease in the hepatic phosphorylation of mammalian target of rapamycin complex C1 (mTORC1) and p70 S6 kinase 1 (S6K1) expressions to improve insulin resistance but also a reduction in hepatic sterol regulatory element binding protein (SREBP)-1c expressions, and suppression of ACC activity, thus resulting in the decreased fatty acid synthesis but elevated hepatic peroxisome proliferator-activated receptor (PPAR) α and SREBP-2 expressions, resulting in lowering TG and TC concentrations. Our results demonstrated that EPE improves insulin resistance and ameliorates hyperlipidemia in HFD mice.
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(This article belongs to the Section Molecular Pharmacology)
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Open AccessReview
Dealkylation of Macromolecules by Eukaryotic α-Ketoglutarate-Dependent Dioxygenases from the AlkB-like Family
by
Anastasiia T. Davletgildeeva and Nikita A. Kuznetsov
Curr. Issues Mol. Biol. 2024, 46(9), 10462-10491; https://doi.org/10.3390/cimb46090622 - 20 Sep 2024
Abstract
Alkylating modifications induced by either exogenous chemical agents or endogenous metabolites are some of the main types of damage to DNA, RNA, and proteins in the cell. Although research in recent decades has been almost entirely devoted to the repair of alkyl and
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Alkylating modifications induced by either exogenous chemical agents or endogenous metabolites are some of the main types of damage to DNA, RNA, and proteins in the cell. Although research in recent decades has been almost entirely devoted to the repair of alkyl and in particular methyl DNA damage, more and more data lately suggest that the methylation of RNA bases plays an equally important role in normal functioning and in the development of diseases. Among the most prominent participants in the repair of methylation-induced DNA and RNA damage are human homologs of Escherichia coli AlkB, nonheme Fe(II)/α-ketoglutarate-dependent dioxygenases ABH1–8, and FTO. Moreover, some of these enzymes have been found to act on several protein targets. In this review, we present up-to-date data on specific features of protein structure, substrate specificity, known roles in the organism, and consequences of disfunction of each of the nine human homologs of AlkB. Special attention is given to reports about the effects of natural single-nucleotide polymorphisms on the activity of these enzymes and to potential consequences for carriers of such natural variants.
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(This article belongs to the Special Issue DNA Damage and Repair in Health and Diseases)
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Hyaluronic Acid in Nanopharmaceuticals: An Overview
by
Sina Matalqah, Zainab Lafi and Sara Yousef Asha
Curr. Issues Mol. Biol. 2024, 46(9), 10444-10461; https://doi.org/10.3390/cimb46090621 - 20 Sep 2024
Abstract
Hyaluronic acid (HA) is a naturally occurring, long, unbranched polysaccharide that plays a critical role in maintaining skin structure and hydration. Its unique properties make it a valuable component in the field of nanopharmaceuticals. The combination of HA into nanopharmaceuticals enhances its ability
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Hyaluronic acid (HA) is a naturally occurring, long, unbranched polysaccharide that plays a critical role in maintaining skin structure and hydration. Its unique properties make it a valuable component in the field of nanopharmaceuticals. The combination of HA into nanopharmaceuticals enhances its ability to interact with various therapeutic agents, improving the delivery and efficacy of drugs. HA-based nanoparticles, including solid lipid nanoparticles, and polymeric nanogels, offer controlled release, enhanced stability, and targeted delivery of therapeutic agents. These innovations significantly improve therapeutic outcomes and reduce side effects, making HA an essential tool in modern medicine. In general, HA-modified liposomes enhance drug encapsulation and targeting, while HA-modified solid lipid nanoparticles (SLNs) provide a solid lipid core for drug encapsulation, offering controlled release and stability. This article provides an overview of the potential applications and recent advancements of HA in nanopharmaceuticals, emphasizing its significant impact on the evolving field of targeted drug delivery and advanced therapeutic strategies. By delving into the unique properties of HA and its compatibility with various therapeutic agents, this review underscores the promising potential of HA in revolutionizing nanopharmaceuticals.
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(This article belongs to the Special Issue Effects of Nanoparticles on Living Organisms 2.0)
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RNA Sequencing of Sperm from Healthy Cattle and Horses Reveals the Presence of a Large Bacterial Population
by
Paula Navarrete-López, Victoria Asselstine, María Maroto, Marta Lombó, Ángela Cánovas and Alfonso Gutiérrez-Adán
Curr. Issues Mol. Biol. 2024, 46(9), 10430-10443; https://doi.org/10.3390/cimb46090620 - 19 Sep 2024
Abstract
RNA molecules within ejaculated sperm can be characterized through whole-transcriptome sequencing, enabling the identification of pivotal transcripts that may influence reproductive success. However, the profiling of sperm transcriptomes through next-generation sequencing has several limitations impairing the identification of functional transcripts. In this study,
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RNA molecules within ejaculated sperm can be characterized through whole-transcriptome sequencing, enabling the identification of pivotal transcripts that may influence reproductive success. However, the profiling of sperm transcriptomes through next-generation sequencing has several limitations impairing the identification of functional transcripts. In this study, we explored the nature of the RNA sequences present in the sperm transcriptome of two livestock species, cattle and horses, using RNA sequencing (RNA-seq) technology. Through processing of transcriptomic data derived from bovine and equine sperm cell preparations, low mapping rates to the reference genomes were observed, mainly attributed to the presence of ribosomal RNA and bacteria in sperm samples, which led to a reduced sequencing depth of RNAs of interest. To explore the presence of bacteria, we aligned the unmapped reads to a complete database of bacterial genomes and identified bacteria-associated transcripts which were characterized. This analysis examines the limitations associated with sperm transcriptome profiling by reporting the nature of the RNA sequences among which bacterial RNA was found. These findings can aid researchers in understanding spermatozoal RNA-seq data and pave the way for the identification of molecular markers of sperm performance.
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(This article belongs to the Special Issue The Contribution and Application of Molecular Biology in the Applied Biosciences — Focusing on Medicine, Biomaterials and Tissue Engineering Fields)
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