Current Issues in Molecular Biology

26 pages, 19818 KiB

Open AccessArticle

Evodiamine Boosts AR Expression to Trigger Senescence and Halt Proliferation in OSCC Cells

by Gang Chen, Hong-Liang Du, Jia-Nan Liu, Jie Cheng, Jing Chen, Xiao-Yang Yin, Hu-Lai Wei and Jing Wang

Curr. Issues Mol. Biol. 2025, 47(7), 558; https://doi.org/10.3390/cimb47070558 - 17 Jul 2025

Abstract

Oral squamous cell carcinoma (OSCC), an aggressive and poorly prognosed subtype of head and neck squamous cell carcinoma (HNSCC), has prompted urgent calls for innovative therapeutic approaches. Evodiamine (EVO), a natural alkaloid extracted from the Chinese herb Evodia rutaecarpa, has demonstrated significant [...] Read more.

Oral squamous cell carcinoma (OSCC), an aggressive and poorly prognosed subtype of head and neck squamous cell carcinoma (HNSCC), has prompted urgent calls for innovative therapeutic approaches. Evodiamine (EVO), a natural alkaloid extracted from the Chinese herb Evodia rutaecarpa, has demonstrated significant potential in curbing tumor cell proliferation and slowing tumor expansion. However, its specific effects on cell senescence within the context of OSCC have remained shrouded in uncertainty. This study delves into the mechanisms of EVO’s impact on OSCC by harnessing databases such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and CellAge to pinpoint potential targets and carry out in-depth bioinformatics analysis. The findings reveal that EVO can markedly enhance the expression of the androgen receptor (AR) in OSCC cells, inducing cellular senescence and thereby inhibiting tumor progression. Furthermore, the research indicates that AR expression is considerably lower in OSCC tissues than in normal tissues. This low expression of AR in tumor tissues is closely associated with advanced clinical stages and unfavorable prognoses in HNSCC patients. These discoveries open up new avenues for therapeutic strategies, and suggest that AR holds promise as a potential therapeutic target for OSCC, and EVO may amplify its antitumor effects by enhancing AR-mediated cellular senescence in the treatment of OSCC. Full article

(This article belongs to the Section Molecular Medicine)

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15 pages, 709 KiB

Open AccessArticle

MMP-9 Activation via ROS/NF-κB Signaling in Colorectal Cancer Progression: Molecular Insights and Prognostic–Therapeutic Perspectives

by Andrej Veljkovic, Goran Stanojevic, Branko Brankovic, Stefanos Roumeliotis, Konstantinos Leivaditis, Branka Djordjevic, Xiaobo Li, Aleksandra Klisic, Jovan Hadzi-Djokic and Gordana Kocic

Curr. Issues Mol. Biol. 2025, 47(7), 557; https://doi.org/10.3390/cimb47070557 - 17 Jul 2025

Abstract

Colorectal cancer (CRC) is characterized by complex interactions between inflammation, oxidative stress, and extracellular matrix remodeling. Recent studies have highlighted the significance of the reactive oxygen species (ROS)–nuclear factor kappa B (NF-κB)–matrix metalloproteinase-9 (MMP-9) axis in promoting tumor invasion and metastasis in CRC, [...] Read more.

Colorectal cancer (CRC) is characterized by complex interactions between inflammation, oxidative stress, and extracellular matrix remodeling. Recent studies have highlighted the significance of the reactive oxygen species (ROS)–nuclear factor kappa B (NF-κB)–matrix metalloproteinase-9 (MMP-9) axis in promoting tumor invasion and metastasis in CRC, linking oxidative stress with inflammatory signaling and extracellular matrix degradation. In this study, we analyzed the concentration of advanced oxidation protein products (AOPPs), expression of NF-κB, and the activity of MMP-9 in tumor tissue, adjacent tissue, and healthy control colon tissue. Tissue specimens were collected from 50 patients with primary CRC following surgical resection. The analyses were performed using appropriate and validated biochemical methods, including ELISA, spectrophotometry, and indirect immunofluorescence. Significantly higher levels of all three markers were observed in tumor tissue compared to controls. Additionally, adjacent tissue exhibited elevated NF-κB expression and MMP-9 activity when compared to healthy colon tissue. AOPP levels correlated strongly with MMP-9 activity, highlighting the role of oxidative stress in the activation of MMP-9. MMP-9 demonstrated the highest predictive value for CRC, emphasizing its potential as a diagnostic and theranostic marker. Our findings support the hypothesis that the ROS–NF-κB–MMP-9 axis plays an important role in CRC progression, particularly during stages T2 and T3. Targeting this pathway may offer new therapeutic strategies for limiting tumor invasion and recurrence. Moreover, ensuring adequate surgical resection margins is crucial to optimizing treatment outcomes. Full article

(This article belongs to the Special Issue Future Challenges of Targeted Therapy of Cancers: 2nd Edition)

23 pages, 1102 KiB

Open AccessReview

Protective Potential of Satureja montana-Derived Polyphenols in Stress-Related Central Nervous System Disorders, Including Dementia

by Stela Dragomanova, Lyubka Tancheva, Silviya Abarova, Valya B. Grigorova, Valentina Gavazova, Dana Stanciu, Svetlin Tzonev, Vladimir Prandjev and Reni Kalfin

Curr. Issues Mol. Biol. 2025, 47(7), 556; https://doi.org/10.3390/cimb47070556 - 17 Jul 2025

Abstract

Satureja montana (SM) is acknowledged as a highly pharmacologically important species within the vast Lamiaceae family, indigenous to the Balkan area. Traditionally, this plant has been employed as a culinary spice, especially in Bulgarian gastronomy. Additionally, it is widely recognized that mental [...] Read more.

Satureja montana (SM) is acknowledged as a highly pharmacologically important species within the vast Lamiaceae family, indigenous to the Balkan area. Traditionally, this plant has been employed as a culinary spice, especially in Bulgarian gastronomy. Additionally, it is widely recognized that mental health is affected by the nature and quality of dietary consumption. Results: Ethnopharmacological research underscores the potential of SM in influencing various chronic ailments, including depression and anxiety. This plant is distinguished by a rich variety of secondary metabolites that display a broad spectrum of biological activities, such as antioxidant, antidiabetic, anti-inflammatory, analgesic, antibacterial, antiviral, and antifungal effects. Particularly, two of its active phenolic compounds, rosmarinic acid and carvacrol, reveal notable anxiolytic and antidepressive properties. This review aims to explore the capacity of SM to improve mental health through its plentiful phenolic components. Recent studies indicate their efficacy in addressing Alzheimer’s-type dementia. A notable correlation exists among depression, anxiety, and cognitive decline, which includes dementia. Considering that Alzheimer’s disease (AD) is a multifaceted condition, it requires multi-targeted therapeutic strategies for both prevention and management. Conclusions: Satureja montana is recognized as potential candidate for both the prevention and management of various mental health disorders, including dementia. Full article

(This article belongs to the Special Issue The Modulatory Effects of Plants with Therapeutic Potential in Neuropsychiatric Disorder)

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15 pages, 13730 KiB

Open AccessArticle

IGFBP5 Promotes Atherosclerosis in APOE^−/− Mice Through Phenotypic Transformation of VSMCs

by Aoqi Xiang, Hua Guan, Peihong Su, Lusha Zhang, Xiaochang Chen and Qi Yu

Curr. Issues Mol. Biol. 2025, 47(7), 555; https://doi.org/10.3390/cimb47070555 - 17 Jul 2025

Abstract

Atherosclerosis constitutes a pathological process underlying cardiovascular diseases. There is growing evidence that IGFBP5 is a causative factor, although the conclusions of different studies are inconsistent. The present study aims to confirm the role and mechanism of IGFBP5 in atherosclerosis. The expression of [...] Read more.

Atherosclerosis constitutes a pathological process underlying cardiovascular diseases. There is growing evidence that IGFBP5 is a causative factor, although the conclusions of different studies are inconsistent. The present study aims to confirm the role and mechanism of IGFBP5 in atherosclerosis. The expression of IGFBP5 was induced in the skeletal muscle of male ApoE^−/− mice, an atherosclerosis model, using adeno-associated virus, resulting in elevated circulating IGFBP5 levels. Changes in blood lipids were detected, and pathological changes in the aorta were observed. Analysis of IGFBP5 function using RNA sequencing and validation were performed in a mouse aortic smooth muscle cell line. The results demonstrated that IGFBP5 overexpression exacerbated the development of aortic lesions in this murine models without any discernible alterations in lipid profile parameters; the arterial transcriptomic landscape revealed that heightened IGFBP5 levels predominantly influenced pathways governing smooth muscle cell proliferation and motility. In vitro experimentation corroborated these findings, showcasing the stimulatory effect of IGFBP5 on VSMC (vascular smooth muscle cell) proliferation and migration, provoking a transition toward a proliferative phenotype. IGFBP5 promotes atherosclerosis in ApoE^−/− mice through the phenotypic transformation of VSMCs. This finding suggests that IGFBP5 has the potential to serve as an indicator of atherosclerosis diagnosis and a target for therapeutic interventions in the future. Full article

(This article belongs to the Special Issue Molecules at Play in Cardiovascular Diseases)

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21 pages, 2245 KiB

Open AccessReview

Epigenetic Mechanisms in Apis melifera: From Development to Environmental Adaptation

by Xiexin Hu, Jing Xu and Kang Wang

Curr. Issues Mol. Biol. 2025, 47(7), 554; https://doi.org/10.3390/cimb47070554 - 17 Jul 2025

Abstract

Epigenetics, as an important scientific field that bridges genomic function and phenotypic plasticity, increasingly demonstrates its value in bee research. In recent years, with the rapid development of omics technologies, there have been significant advancements in the study of epigenetics in honeybees. This [...] Read more.

Epigenetics, as an important scientific field that bridges genomic function and phenotypic plasticity, increasingly demonstrates its value in bee research. In recent years, with the rapid development of omics technologies, there have been significant advancements in the study of epigenetics in honeybees. This article reviews the role of epigenetic regulation in the development, behavioral regulation, and immune response of honeybee larvae from the perspectives of DNA methylation, histone modification, and non-coding RNA. With the continuous deepening of related research, honeybee epigenetics not only opens new paths for understanding the formation mechanisms of complex traits in social insects but also provides solid theoretical support and innovative perspectives for the study of social insects and beekeeping practices. These insights also inform sustainable beekeeping practices. Full article

(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)

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16 pages, 1945 KiB

Open AccessArticle

Assembly and Comparative Analysis of Complete Mitochondrial Genome Sequence of Endangered Medicinal Plant Trichopus zeylanicus

by Biju Vadakkemukadiyil Chellappan, P. R. Shidhi, Anu Sasi, Rashid Ismael Hag Ibrahim and Hamad Abu Zahra

Curr. Issues Mol. Biol. 2025, 47(7), 553; https://doi.org/10.3390/cimb47070553 - 16 Jul 2025

Abstract

Plant mitochondrial genomes exhibit extensive size variability and structural complexity. Here, we report the complete mitochondrial genome of Trichopus zeylanicus, an endemic medicinal plant from the Western Ghats. The mitochondrial genome was assembled using a combination of Illumina short-read and PacBio long-read [...] Read more.

Plant mitochondrial genomes exhibit extensive size variability and structural complexity. Here, we report the complete mitochondrial genome of Trichopus zeylanicus, an endemic medicinal plant from the Western Ghats. The mitochondrial genome was assembled using a combination of Illumina short-read and PacBio long-read sequencing technologies, followed by extensive annotation and comparative analysis. The circular mitogenome spans 709,127 bp with a GC content of 46%, encoding 32 protein-coding genes, 17 tRNAs, and three rRNAs. Comparative analysis with other monocot mitochondrial genomes revealed conserved gene clusters but also significant lineage-specific rearrangements. Despite genome size similarities, T. zeylanicus displayed marked divergence in gene order, suggesting that genome size does not necessarily correlate with structural conservation. The genome contains 6.7% chloroplast-derived sequences and 324 predicted RNA-editing sites, predominantly in the first and second codon positions. Phylogenetic analysis based on mitochondrial genes placed T. zeylanicus as a distinct lineage within Dioscoreales, supporting its evolutionary uniqueness. This work provides the first mitogenomic resource for Dioscoreales and advances our understanding of mitochondrial diversity and evolution in monocots. Full article

(This article belongs to the Special Issue Technological Advances Around Next-Generation Sequencing Application)

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19 pages, 5038 KiB

Open AccessArticle

A Novel Hypoxia-Immune Signature for Gastric Cancer Prognosis and Immunotherapy: Insights from Bulk and Single-Cell RNA-Seq

by Mai Hanh Nguyen, Hoang Dang Khoa Ta, Doan Phuong Quy Nguyen, Viet Huan Le and Nguyen Quoc Khanh Le

Curr. Issues Mol. Biol. 2025, 47(7), 552; https://doi.org/10.3390/cimb47070552 - 16 Jul 2025

Abstract

Background: Hypoxia and immune components significantly shape the tumor microenvironment and influence prognosis and immunotherapy response in gastric cancer (GC). This study aimed to develop hypoxia- and immune-related gene signatures for prognostic evaluation in GC. Methods: Transcriptomic data from TCGA-STAD were [...] Read more.

Background: Hypoxia and immune components significantly shape the tumor microenvironment and influence prognosis and immunotherapy response in gastric cancer (GC). This study aimed to develop hypoxia- and immune-related gene signatures for prognostic evaluation in GC. Methods: Transcriptomic data from TCGA-STAD were integrated with hypoxia- and immune-related genes from InnateDB and MSigDB. A prognostic gene signature was constructed using Cox regression analyses and validated on an independent GSE84437 cohort and single-cell RNA dataset. We further analyzed immune cell infiltration, molecular characteristics of different risk groups, and their association with immunotherapy response. Single-cell RNA-seq data from the TISCH database were used to explore gene expression patterns across cell types. Results: Five genes (TGFB3, INHA, SERPINE1, GPC3, SRPX) were identified. The risk score effectively stratified patients by prognosis, with the high-risk group showing lower overall survival and lower T-cell expression. The gene signature had an association with immune suppression, ARID1A mutation, EMT features, and poorer response to immunotherapy. Gene signature, especially SRPX was enriched in fibroblasts. Conclusions: We developed a robust hypoxia- and immune-related gene signature that predicts prognosis and may help guide immunotherapy strategies for GC patients. Full article

(This article belongs to the Special Issue Linking Genomic Changes with Cancer in the NGS Era, 2nd Edition)

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11 pages, 2777 KiB

Open AccessArticle

Bioinformatics Analysis and Functional Verification of Phytoene Synthase Gene PjPSY1 of Panax japonicus C. A. Meyer

by Tingting Tang, Rui Jin, Xilun Huang, E Liang and Lai Zhang

Curr. Issues Mol. Biol. 2025, 47(7), 551; https://doi.org/10.3390/cimb47070551 - 16 Jul 2025

Abstract

Phytoene synthase (PSY) is a multimeric enzyme that serves as the first enzyme in carotenoid synthesis within plant tissues and plays a crucial role in the production of carotenoids in plants. To understand the function of the PSY gene in Panax japonicus C. [...] Read more.

Phytoene synthase (PSY) is a multimeric enzyme that serves as the first enzyme in carotenoid synthesis within plant tissues and plays a crucial role in the production of carotenoids in plants. To understand the function of the PSY gene in Panax japonicus C. A. Meyer. fruit, the gene’s transcript was obtained by analyzing the transcriptome sequencing data of Panax japonicus fruit. The CDS sequence of the gene was cloned from Panax japonicus fruit using the RT-PCR cloning technique and named PjPSY1, which was then subjected to biosynthetic analysis and functional verification. The results showed that the open reading frame of the gene was 1269 bp, encoding 423 amino acids, with a protein molecular mass of 47,654.67 KDa and an isoelectric point (pI) of 8.63; the protein encoded by these amino acids was hydrophilic and localized in chloroplasts, and its three-dimensional structure was predicted by combining the pymol software to annotate the N site of action and active centre of the protein. Phylogenetic analysis demonstrated that PjPSY1 had the closest affinity to DcPSY from Daucus carota. Overexpression of PjPSY1 led to a significant increase in the content of carotenoid-related monomers in Arabidopsis thaliana, with Violaxanthin being synthesized in transgenic Arabidopsis thaliana but not in wild-type Arabidopsis thaliana. The PjPSY1 clone obtained in this study was able to promote carotenoid synthesis in the fruits of Panax japonicus, revealing that the mode of action of PjPSY1 in the carotenoid biosynthesis pathway of Panax japonicus fruits has a positive regulatory effect. Full article

(This article belongs to the Section Bioinformatics and Systems Biology)

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13 pages, 6330 KiB

Open AccessArticle

Erythroblasts Promote the Development of a Suppressive Lymphocyte Phenotype via Treg Induction and PD1 Upregulation on the Surfaces of B-Cells: A Study on the Subpopulation-Specific Features of Erythroblasts

by Kirill Nazarov, Roman Perik-Zavodskii, Julia Shevchenko and Sergey Sennikov

Curr. Issues Mol. Biol. 2025, 47(7), 550; https://doi.org/10.3390/cimb47070550 - 15 Jul 2025

Abstract

This study identifies the novel effects of soluble factors derived from murine erythroblasts on lymphoid cell phenotypes. These effects were observed following the treatment of splenic mononuclear cells with erythroblast-conditioned media received from both healthy mice and mice subjected to hematopoiesis-activating conditions (hypoxia, [...] Read more.

This study identifies the novel effects of soluble factors derived from murine erythroblasts on lymphoid cell phenotypes. These effects were observed following the treatment of splenic mononuclear cells with erythroblast-conditioned media received from both healthy mice and mice subjected to hematopoiesis-activating conditions (hypoxia, blood loss, and hemolytic anemia), suggesting a common mechanism of action. Using flow cytometry, we elucidated that erythroblast-derived soluble products modulate T cell differentiation by promoting Treg development and increasing PD-1 surface expression on B cells. The immunoregulatory potential of erythroblasts is subpopulation-dependent: CD45+ erythroblasts respond to hemolytic stress by upregulating the surface expression of immunosuppressive molecules PDL1 and Galectin-9, while CD45- erythroblasts primarily increase TGFb production. These findings highlight the regulatory role of erythroblasts in modulating immune responses. Full article

(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)

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18 pages, 4537 KiB

Open AccessArticle

Colostrum-Derived Exosomal Lactoferrin Promotes Skin Fibroblast Regeneration by Suppressing Inflammatory Responses

by Chu-Hsun Cheng, Wei-Jer Hong, Chien-Nien Li, Yung-Hsueh Huang, Jeng-Haw Tsai, Chih-Yuan Huang, Jen-Chin Wu, Chan-Yen Kuo and Wen-Chun Kuo

Curr. Issues Mol. Biol. 2025, 47(7), 549; https://doi.org/10.3390/cimb47070549 - 15 Jul 2025

Abstract

Lactoferrin (LF), a multifunctional glycoprotein found abundantly in bovine colostrum, is known for its regenerative and anti-inflammatory properties. In this study, we investigated the wound healing and immunomodulatory effects of colostrum-derived exosome-encapsulated lactoferrin (EV-exoLF) on dermal fibroblasts. EV-exoLF was isolated and characterized via [...] Read more.

Lactoferrin (LF), a multifunctional glycoprotein found abundantly in bovine colostrum, is known for its regenerative and anti-inflammatory properties. In this study, we investigated the wound healing and immunomodulatory effects of colostrum-derived exosome-encapsulated lactoferrin (EV-exoLF) on dermal fibroblasts. EV-exoLF was isolated and characterized via nanoparticle tracking analysis and flow cytometry. Functional assays demonstrated that EV-exoLF significantly promoted fibroblast viability and migration in both mouse NIH/3T3 and human HS-68 cell lines. Furthermore, EV-exoLF reduced the expression of pro-inflammatory cytokines (IL-1 and IL-6) and phosphorylated JNK in lipopolysaccharide (LPS)-treated fibroblasts. These findings suggest that EV-exoLF not only enhances fibroblast-mediated wound closure but also mitigates inflammation, highlighting its therapeutic potential in skin regeneration. Colostrum-derived exosomal lactoferrin may serve as a promising natural, cell-free strategy for managing inflammatory skin conditions and improving wound healing outcomes. Full article

(This article belongs to the Special Issue The Role of Bioactives in Inflammation, 2nd Edition)

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26 pages, 5612 KiB

Open AccessArticle

The Nutritional Gene Expression Regulation Potential of a Lysolecithin-Based Product

by Veerle Van Hoeck, Riet Spaepen and Bart Forier

Curr. Issues Mol. Biol. 2025, 47(7), 548; https://doi.org/10.3390/cimb47070548 - 15 Jul 2025

Abstract

Lysolecithin is a performance-enhancing product for livestock. Lysolecithins contain functional phospholipids (PLs) and lysophospholipids (LPLs) and have been used in monogastric feed formulations because they can enhance lipid emulsification, digestion, and absorption (surface chemistry). Another underexplored aspect is that lysolecithin mixtures can serve [...] Read more.

Lysolecithin is a performance-enhancing product for livestock. Lysolecithins contain functional phospholipids (PLs) and lysophospholipids (LPLs) and have been used in monogastric feed formulations because they can enhance lipid emulsification, digestion, and absorption (surface chemistry). Another underexplored aspect is that lysolecithin mixtures can serve as signaling via so-called nutritional gene expression-regulating action. The scope of this study was to fully understand the potential of a lysolecithin source derived from soybeans to influence intestinal nutrient transport in the intestinal tract. In this context, in vitro cell culture data with intestinal Caco-2 cells revealed that a lysolecithin-based product can significantly improve intestinal cell viability. Furthermore, a Transwell culture experiment showed that lysolecithins can significantly trigger gene expression. The most significantly affected genes could be correlated with G-coupled protein cascades. Enrichment analyses showed that amino acid transport and lipid metabolism pathways are significantly affected. Furthermore, the polarized cell culture revealed that the studied lysolecithin could affect the abundance of metabolites/nutrients in the basolateral compartment when applied apically, indicating that its action exceeds surface chemistry. In conclusion, the data on intestinal cell viability, gene expression, and metabolite abundance seem to reveal the bioactivities of lysolecithin. The latter data suggest that the specific lysolecithin source used here is more than a biosurfactant; more specifically, it seems to be a potent bioactive mixture of amphiphilic compounds triggering cell signaling pathways. Full article

(This article belongs to the Section Bioinformatics and Systems Biology)

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17 pages, 1839 KiB

Open AccessReview

The Clock and the Brain: Circadian Rhythm and Alzheimer’s Disease

by Samaneh Ghorbani Shirkouhi, Ashkan Karimi, Seyed Sepehr Khatami, Ashkan Asgari Gashtrodkhani, Farzin Kamari, Morten Blaabjerg and Sasan Andalib

Curr. Issues Mol. Biol. 2025, 47(7), 547; https://doi.org/10.3390/cimb47070547 - 15 Jul 2025

Abstract

Alzheimer’s Disease (AD) is the most common type of dementia. The circadian system, which is controlled by the master clock in the Suprachiasmatic Nucleus (SCN) of the hypothalamus, is crucial for various physiological processes. Studies have shown that changes in the circadian rhythms [...] Read more.

Alzheimer’s Disease (AD) is the most common type of dementia. The circadian system, which is controlled by the master clock in the Suprachiasmatic Nucleus (SCN) of the hypothalamus, is crucial for various physiological processes. Studies have shown that changes in the circadian rhythms can deteriorate neurodegenerative diseases. Changes in the SCN are associated with cognitive decline in AD. The cognitive impairments in AD, especially memory dysfunctions, may be related to Circadian Rhythm Disturbances (CRDs). Moreover, rhythmic expression of clock genes is disrupted in AD patients. There is a circadian pattern of inflammatory processes in AD, and dysregulation of core clock genes promotes neuroinflammation. The present narrative review addresses the intricate link between CRDs and AD, revisiting the relevant cellular and molecular mechanisms. The association between CRDs and AD highlights the need for further investigation of the underlying mechanisms. Full article

(This article belongs to the Special Issue The Role of Neuroinflammation in Neurodegenerative Diseases)

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35 pages, 10190 KiB

Open AccessArticle

Molecular Mechanisms of Lobelia nummularia Extract in Breast Cancer: Targeting EGFR/TP53 and PI3K-AKT-mTOR Signaling via ROS-Mediated Apoptosis

by Fahu Yuan, Yu Qiao, Zhongqiang Chen, Huihuang He, Fuyan Wang and Jiangyuan Chen

Curr. Issues Mol. Biol. 2025, 47(7), 546; https://doi.org/10.3390/cimb47070546 - 14 Jul 2025

Abstract

Lobelia nummularia Lam. is a traditional medicinal herb of which the anticancer mechanisms remain largely unexplored. Here, we demonstrated that its ethanolic extract (LNE) exerts potent anti-breast cancer activity by inducing ROS-dependent mitochondrial apoptosis in MDA-MB-231 cells, a mechanism confirmed via rescue experiments [...] Read more.

Lobelia nummularia Lam. is a traditional medicinal herb of which the anticancer mechanisms remain largely unexplored. Here, we demonstrated that its ethanolic extract (LNE) exerts potent anti-breast cancer activity by inducing ROS-dependent mitochondrial apoptosis in MDA-MB-231 cells, a mechanism confirmed via rescue experiments with the antioxidant N-acetylcysteine (NAC). This pro-apoptotic program is driven by a dual mechanism: potent suppression of the pro-survival EGFR/PI3K/AKT signaling pathway and simultaneous activation of the TP53-mediated apoptotic cascade, culminating in the cleavage of executor caspase-3. Phytochemical analysis identified numerous flavonoids, and quantitative HPLC confirmed that key bioactive compounds, including luteolin and apigenin, are substantially present in the extract. These mechanisms translated to significant in vivo efficacy, where LNE administration suppressed primary tumor growth and lung metastasis in a 4T1 orthotopic model in BALB/c mice. Furthermore, a validated molecular docking protocol provided a plausible structural basis for these multi-target interactions. Collectively, this study provides a comprehensive, multi-layered validation of LNE’s therapeutic potential, establishing it as a mechanistically well-defined candidate for natural product-based anticancer drug discovery. Full article

(This article belongs to the Special Issue Molecular Insights: Mechanisms Underlying the Biological Activities of Natural Products)

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16 pages, 3716 KiB

Open AccessArticle

Genome-Wide Analysis of Oxidosqualene Cyclase Genes in Artemisia annua: Evolution, Expression, and Potential Roles in Triterpenoid Biosynthesis

by Changfeng Guo, Si Xu and Xiaoyun Guo

Curr. Issues Mol. Biol. 2025, 47(7), 545; https://doi.org/10.3390/cimb47070545 - 14 Jul 2025

Abstract

Plant triterpenoids are structurally diverse specialized metabolites with significant ecological, medicinal, and agricultural importance. Oxidosqualene cyclases (OSCs) catalyze the crucial cyclization step in triterpenoid biosynthesis, generating the fundamental carbon skeletons that determine their structural diversity and biological functions. Genome-wide identification of OSC genes [...] Read more.

Plant triterpenoids are structurally diverse specialized metabolites with significant ecological, medicinal, and agricultural importance. Oxidosqualene cyclases (OSCs) catalyze the crucial cyclization step in triterpenoid biosynthesis, generating the fundamental carbon skeletons that determine their structural diversity and biological functions. Genome-wide identification of OSC genes was performed using bioinformatics tools, including HMMER and BLASTP, followed by phylogenetic analysis, gene structure analysis, conserved domain and motifs identification, cis-regulatory element prediction, protein–protein interaction analysis, and expression profiling using publicly available transcriptome data from UV-B treated A. annua six-week-old seedlings. We identified 24 AaOSC genes, classified into CAS, LAS, LUS, and unknown subfamilies. Phylogenetic analysis revealed evolutionary relationships with OSCs from other plant species. Gene structure analysis showed variations in exon–intron organization. Promoter analysis identified cis-regulatory elements related to light responsiveness, plant growth and development, hormone signaling, and stress response. Expression profiling revealed differential expression patterns of AaOSC genes under UV-B irradiation. This genome-wide characterization provides insights into the evolution and functional diversification of the OSC gene family in A. annua. The identified AaOSC genes and their regulatory elements lay the foundation for future studies aimed at manipulating triterpenoid biosynthesis for medicinal and biotechnological applications, particularly focusing on enhancing stress tolerance and artemisinin production. Full article

(This article belongs to the Special Issue Functional Genomics and Comparative Genomics Analysis in Plants, 3rd Edition)

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15 pages, 2126 KiB

Open AccessReview

Prognostic Value of the Immunohistochemical Detection of Cellular Components of the Tumor Microenvironment in Oral Squamous Cell Carcinoma: A Systematic Review

by Hannah Gil de Farias Morais, Caroline Fernandes da Costa, Maurília Raquel de Souto Medeiros, Bárbara de Assis Araújo, Everton Freitas de Morais, Ricardo D. Coletta and Roseana de Almeida Freitas

Curr. Issues Mol. Biol. 2025, 47(7), 544; https://doi.org/10.3390/cimb47070544 - 12 Jul 2025

Abstract

This study aims to investigate the prognostic impact of cellular components of the tumor microenvironment (TME), analyzed through immunohistochemistry, in oral squamous cell carcinoma (OSCC). This review was conducted following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). [...] Read more.

This study aims to investigate the prognostic impact of cellular components of the tumor microenvironment (TME), analyzed through immunohistochemistry, in oral squamous cell carcinoma (OSCC). This review was conducted following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Searches were performed in EMBASE, Medline/PubMed, Cochrane Collaboration Library, Web of Science, ScienceDirect, Scopus, and Google Scholar. After applying the study criteria, 59 articles were included, involving the analysis of cancer-associated fibroblasts (CAFs), immune cells, and endothelial cells. It was found that TME rich in α-SMA-positive CAFs, tumor-associated macrophages, and dendritic cells contribute to the invasion and progression of OSCC, resulting in a poorer prognosis. In contrast, the presence of high amounts of NK CD57⁺ cells, CD8⁺/CD45RO⁺ T cells, and PNAd⁺ endothelial cells are associated with anti-tumor immune responses in OSCC and improved survival rates. CD3⁺ and CD4⁺ T cells, Treg cells, B cells, and mast cells have shown little to no evidence of prognostic utility. Several stromal components of TME were found to have a strong impact on the aggressiveness of OSCC, reaffirming the potential use of these biomarkers as prognostic tools and therapeutic targets. Full article

(This article belongs to the Special Issue Oral Cancer: Prophylaxis, Etiopathogenesis and Treatment, 2nd Edition)

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22 pages, 12756 KiB

Open AccessArticle

The Antidiabetic Mechanisms of Cinnamon Extract: Insights from Network Pharmacology, Gut Microbiota, and Metabolites

by Rong Wang, Kuan Yang, Xuefeng Liu, Yiye Zhang, Yunmei Chen, Nana Wang, Lili Yu, Shaojing Liu, Yaqi Hu and Bei Qin

Curr. Issues Mol. Biol. 2025, 47(7), 543; https://doi.org/10.3390/cimb47070543 - 12 Jul 2025

Abstract

The progression of type 2 diabetes mellitus (T2DM) is shaped by a multifaceted interplay among genetic, behavioral, and environmental factors, alongside gut dysbiosis. Cinnamon, being abundant in polyphenols and flavonoids, shows significant antioxidant effects. Studies have substantiated that cinnamon contributes to the management [...] Read more.

The progression of type 2 diabetes mellitus (T2DM) is shaped by a multifaceted interplay among genetic, behavioral, and environmental factors, alongside gut dysbiosis. Cinnamon, being abundant in polyphenols and flavonoids, shows significant antioxidant effects. Studies have substantiated that cinnamon contributes to the management of glucose and lipid metabolism. However, the anti-diabetic efficacy of cinnamon is not completely understood. The objective of this research was to clarify the anti-diabetic mechanism associated with cinnamon extract through a combination of chemical profiling, network pharmacology, and in vivo investigations. The results indicated that 32 chemical ingredients, including quercetin, were identified through UPLC-Q-TOF-MS. Network pharmacology revealed that 471 targets related to 14 compounds were screened. The analysis of GO enrichment revealed that the primary pathways were notably enhanced in the metabolism of insulin and glucose. In vivo analyses showed that cinnamon could effectively alleviate hyperglycemia, insulin resistance, and lipid metabolism abnormalities via increased relative abundance of Akkermansia and Ligilactobacillus at the genus level and a decreased Firmicutes/Bacteroidetes ratio at the phylum level. Moreover, cinnamon reduced the serum levels of lipopolysaccharide (LPS) and proinflammatory cytokines (IL-6 and TNF-α) and significantly increased the colon Zonula occludens-1 (ZO-1) and occludin protein levels. It was also observed that cinnamon improved the fecal SCFA levels (acetic, propionic, butyric, valeric and caproic acid), while also modifying the bile acid (BA) profile and increasing the conjugated-to-unconjugated BA ratio. The Western blotting analysis further demonstrated that cinnamon activated intestinal FXR/FGF15 and hepatic PI3K/AKT signaling pathways. In summary, the finding confirmed that cinnamon ameliorated glucose and lipid metabolism disorders by safeguarding the intestinal barrier and modulating the gut microbiota and metabolites, thereby activating intestinal FXR/FGF15 and hepatic PI3K/AKT signaling pathways. Full article

(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)

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21 pages, 5459 KiB

Open AccessArticle

NAC Gene Family in Lagerstroemia indica: Genome-Wide Identification, Characterization, Expression Analysis, and Key Regulators Involved in Anthocyanin Biosynthesis

by Zilong Gao, Zhuomei Chen, Jinfeng Wang and Weixin Liu

Curr. Issues Mol. Biol. 2025, 47(7), 542; https://doi.org/10.3390/cimb47070542 - 11 Jul 2025

Abstract

NAC (NAM, ATAF1/2, CUC1/2) is a plant-specific transcription factor (TF) family that plays important roles in various physiological and biochemical processes of plants. However, the NAC gene family in Lagerstroemia indica and its role in anthocyanin metabolism are still unexplored. In our study, [...] Read more.

NAC (NAM, ATAF1/2, CUC1/2) is a plant-specific transcription factor (TF) family that plays important roles in various physiological and biochemical processes of plants. However, the NAC gene family in Lagerstroemia indica and its role in anthocyanin metabolism are still unexplored. In our study, a total of 167 NACs were identified in the L. indica genome via genome-wide analysis and bioinformatics techniques. Amino acid sequence analysis showed that all 167 NAC proteins contained a conserved NAM domain. This domain primarily comprised random coils, extended strands, and alpha helices. Most NACs were found on the nucleus and dispersed over 23 of the 24 plant chromosomes. Based on phylogenetic analysis, the NACs can be categorized into ten subgroups. Furthermore, the promoter homeotropic elements predicted the cis-acting elements in the promoters of these genes related to hormones, development, environmental stress response, and other related responses, demonstrating the diverse regulatory mechanisms underlying gene functions. In addition, a co-expression network was established through RNA sequencing. This network helped identify seven key LiNACs, genes related to anthocyanin expression (CHS) and transcription factors (MYB and bHLH). To identify potential anthocyanin regulatory factors present in L. indica petals, protein interaction prediction was performed, which revealed that LiNACs might participate in anthocyanin regulation by interacting with other proteins, such as MYB, ABF, ABI, bZIP, MYC, etc. Our results provided novel insights and could help in the functional identification of LiNACs in L. indica and the regulation of anthocyanin synthesis. Full article

(This article belongs to the Special Issue Molecular Breeding and Genetics Research in Plants, 2nd Edition)

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16 pages, 2901 KiB

Open AccessArticle

Analysis of Pharmacological Activities and Mechanisms of Essential Oil in Flowers of Citrus grandis ‘Tomentosa’ by GC-MS/MS and Network Pharmacology

by Danxi Yan, Shuyi Wen, Mingxia Chen, Jinlan Huang, Guihao Zhang, Renkai Li, Jiamin Lu, Zhongxuan Yao, Fei Gao and Jieshu You

Curr. Issues Mol. Biol. 2025, 47(7), 541; https://doi.org/10.3390/cimb47070541 - 11 Jul 2025

Abstract

According to our research, the flowers from Citrus grandis ‘Tomentosa’ contain rich biologically active essential oil components, but the chemical components and relative pharmacological properties have not been systematically studied. Therefore, the study aimed to identify the essential oil components by GC-MS/MS and [...] Read more.

According to our research, the flowers from Citrus grandis ‘Tomentosa’ contain rich biologically active essential oil components, but the chemical components and relative pharmacological properties have not been systematically studied. Therefore, the study aimed to identify the essential oil components by GC-MS/MS and explore the pharmacological activity and mechanism of these essential oil components by a network pharmacology approach. Finally, GC-MS/MS analysis identified 43 essential oil components, which corresponded to 739 potential targets. GO analysis results showed that 12, 18, and 12 entries were related to biological processes, cellular components, and molecular functions, respectively. A total of 120 pathways were obtained based on KEGG analysis, of which the most important was the adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway. The “active component–target–disease” network further demonstrated these essential oil components’ potential efficacy against pain, tumors, neuropsychiatric diseases, eye diseases, and respiratory diseases, which were highly related to PPARA, GABRA1, PTGS2, and SLC6A2. Experimental validation confirmed that β-caryophyllene, a major constituent, dose-dependently inhibited the proliferation of HT29 and MCF-7 cells (0–320 μM). This study provides a reliable basis for elucidating the pharmacological activity of the essential oil components and related mechanisms, which is beneficial to the comprehensive utilization and development of Citrus grandis ‘Tomentosa’. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Bioactive Compounds in the Management of Human Diseases)

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29 pages, 538 KiB

Open AccessReview

Dynamic Rendition of Adipose Genes Under Epigenetic Regulation: Revealing New Mechanisms of Obesity Occurrence

by Weijing Wen, Simeng Gu, Fanjia Guo, Zhijian Chen, Sujun Yan and Zhe Mo

Curr. Issues Mol. Biol. 2025, 47(7), 540; https://doi.org/10.3390/cimb47070540 - 11 Jul 2025

Abstract

Obesity is a chronic metabolic disorder and a growing global public health challenge, affecting hundreds of millions of individuals worldwide. While diet and physical activity are well-established contributors, increasing evidence underscores the critical role of epigenetic mechanisms in mediating obesity-related processes. Epigenetic modifications—such [...] Read more.

Obesity is a chronic metabolic disorder and a growing global public health challenge, affecting hundreds of millions of individuals worldwide. While diet and physical activity are well-established contributors, increasing evidence underscores the critical role of epigenetic mechanisms in mediating obesity-related processes. Epigenetic modifications—such as DNA methylation, RNA methylation (particularly N6-methyladenosine), histone modifications, non-coding RNAs, and chromatin remodeling—modulate gene expression without altering the DNA sequence. This review aims to provide an overview of the epigenetic mechanisms involved in obesity, with an emphasis on their molecular functions and regulatory networks. Integrating findings from relevant studies, we discuss how these modifications influence obesity-related outcomes through regulating key processes such as adipocyte differentiation and energy metabolism. Advancing our understanding of epigenetic regulation may pave the way for novel, targeted strategies in the prevention and treatment of obesity. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2025)

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