Current Issues in Molecular Biology

40 pages, 2634 KiB

Open AccessReview

Plateau Environment, Gut Microbiota, and Depression: A Possible Concealed Connection?

by Yajun Qiao, Ruiying Cheng, Xiaohui Li, Huimin Zheng, Juan Guo, Lixin Wei, Tingting Gao and Hongtao Bi

Curr. Issues Mol. Biol. 2025, 47(7), 487; https://doi.org/10.3390/cimb47070487 (registering DOI) - 25 Jun 2025

Abstract

Plateau environments present unique mental health challenges owing to stressors including hypoxia, low temperatures, and intense ultraviolet (UV) radiation. These factors induce structural and functional alterations in the gut microbiota, disrupting gut-brain axis homeostasis and contributing to the higher prevalence of depression in [...] Read more.

Plateau environments present unique mental health challenges owing to stressors including hypoxia, low temperatures, and intense ultraviolet (UV) radiation. These factors induce structural and functional alterations in the gut microbiota, disrupting gut-brain axis homeostasis and contributing to the higher prevalence of depression in plateau regions relative to flatland areas. For example, studies report that 28.6% of Tibetan adults and 29.2% of children/adolescents on the Qinghai-Tibet Plateau experience depression, with increasing evidence linking this trend to alterations in the gut microbiota. Dysbiosis contributes to depression through three interconnected mechanisms: (1) Neurotransmitter imbalance: Reduced bacterial diversity impairs serotonin synthesis, disrupting emotional regulation. (2) Immune dysregulation: Compromised gut barrier function allows bacterial metabolites to trigger systemic inflammation via toll-like receptor signaling pathways. (3) Metabolic dysfunction: Decreased short-chain fatty acid levels weaken neuroprotection and exacerbate hypothalamic-pituitary-adrenal axis stress responses. Current interventions—including dietary fiber, probiotics, and fecal microbiota transplantation—aim to restore microbiota balance and increase short-chain fatty acids, alleviating depressive symptoms. However, key knowledge gaps remain in understanding the underlying mechanisms and generating population-specific data. In conclusion, existing evidence indicates an association between plateau environments, the gut microbiota, and depression, but causal relationships and underlying mechanisms require further empirical investigation. Integrating multiomics technologies to systematically explore interactions among high-altitude environments, the microbiota and the brain will facilitate the development of precision therapies such as personalized nutrition and tailored probiotics to protect mental health in high-altitude populations. Full article

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

► Show Figures

Figure 1

12 pages, 2552 KiB

Open AccessArticle

Investigating the Mechanism of Emodin in Rheumatoid Arthritis Through the HIF-1α/NLRP3 Pathway and Mitochondrial Autophagy

by Dehao Du, Linlan Zhou, Jiayu Tian, Lianying Cheng, Han Zhang, Yifu Tang, Zexuan Qiu, Tingdan Zhang and Xiaofeng Rong

Curr. Issues Mol. Biol. 2025, 47(7), 486; https://doi.org/10.3390/cimb47070486 (registering DOI) - 25 Jun 2025

Abstract

In this study, we investigated the inhibitory effects of emodin on pyroptosis in rheumatoid arthritis (RA) synovial cells by modulating the HIF-1α/NLRP3 inflammasome pathway and mitochondrial autophagy. By employing a chemically induced hypoxia model with CoCl₂, we established experimental groups including [...] Read more.

In this study, we investigated the inhibitory effects of emodin on pyroptosis in rheumatoid arthritis (RA) synovial cells by modulating the HIF-1α/NLRP3 inflammasome pathway and mitochondrial autophagy. By employing a chemically induced hypoxia model with CoCl₂, we established experimental groups including normal control, model group, and emodin-treated groups at different concentrations (5 μM, 10 μM, and 20 μM). We optimized the CoCl₂ concentration via CCK-8 assay to ensure cell viability. ELISA, Western blotting, transmission electron microscopy, and immunofluorescence were employed to assess HIF-1α, IL-1β, and IL-18 levels, pyroptosis-related proteins, autophagy markers, and NLRP3 fluorescence intensity. Statistical analysis revealed that increased CoCl₂ concentrations led to a significant cell viability reduction (p < 0.05), with 300 μM CoCl₂ causing ~50% inhibition at 24 h. Transmission electron microscopy confirmed autophagosome formation in emodin-treated groups, while Western blotting showed dose-dependent downregulation of HIF-1α, NLRP3, BNIP3, and related proteins. Immunofluorescence revealed reduced NLRP3 fluorescence intensity with increasing emodin doses (p < 0.05), alongside dose-dependent cell viability recovery (p < 0.05). Our findings demonstrate that emodin alleviates RA synovitis through dual mechanisms: inhibition of mitochondrial autophagy to regulate the balance between mitochondrial autophagy and pyroptosis, and suppression of HIF-1α/NLRP3-mediated pyroptosis signaling, thereby reducing IL-1β and IL-18 release and inhibiting synovial cell proliferation. This study provides innovative approaches for targeted RA therapy. Full article

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

► Show Figures

Figure 1

23 pages, 3705 KiB

Open AccessArticle

Revealing the Multi-Target Mechanisms of Fespixon Cream in Diabetic Foot Ulcer Healing: Integrated Network Pharmacology, Molecular Docking, and Clinical RT-qPCR Validation

by Tianbo Li, Dehua Wei, Jiangning Wang and Lei Gao

Curr. Issues Mol. Biol. 2025, 47(7), 485; https://doi.org/10.3390/cimb47070485 (registering DOI) - 25 Jun 2025

Abstract

Objective: This study aims to elucidate the potential mechanisms by which Fespixon cream promotes diabetic foot ulcer (DFU) healing using network pharmacology, molecular docking, and RT-qPCR validation in clinical tissue samples. Methods: Active components of Fespixon cream were screened from the Traditional Chinese [...] Read more.

Objective: This study aims to elucidate the potential mechanisms by which Fespixon cream promotes diabetic foot ulcer (DFU) healing using network pharmacology, molecular docking, and RT-qPCR validation in clinical tissue samples. Methods: Active components of Fespixon cream were screened from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and relevant literature, and their corresponding targets were standardized using the Universal Protein Resource (UniProt) database. Diabetic foot ulcer (DFU)-related targets were retrieved and filtered from the GeneCards database and the Online Mendelian Inheritance in Man (OMIM) database. The intersection of drug and disease targets was identified, and a protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. The interaction network was visualized using Cytoscape version 3.7.2 software. The potential mechanisms of the shared targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis using R software packages, and results were visualized through Bioinformatics online tools. Molecular docking was performed to validate the binding between key active compounds of Fespixon cream and core DFU targets using AutoDock Vina version 1.1.2 and PyMOL software. Furthermore, RT-qPCR analysis was performed on wound edge tissue samples from DFU patients treated with Fespixon cream to experimentally verify the mRNA expression levels of predicted hub genes. Results: Network pharmacology analysis identified eight active compounds in Fespixon cream, along with 153 potential therapeutic targets related to diabetic foot ulcer (DFU). Among these, 21 were determined as core targets, with the top five ranked by degree value being RAC-αserine/threonine-protein kinase (AKT1), Cellular tumor antigen p53 (TP53), Tumor necrosis factor (TNF), Interleukin-6 (IL6), and Mitogen-activated protein kinase 1 (MAPK1). GO enrichment analysis indicated that the targets of Fespixon cream were primarily involved in various biological processes related to cellular stress responses. KEGG pathway enrichment revealed that these targets were significantly enriched in pathways associated with diabetic complications, atherosclerosis, inflammation, and cancer. Molecular docking confirmed stable binding interactions between the five major active compounds—quercetin, apigenin, rosmarinic acid, salvigenin, and cirsimaritin—and the five core targets (AKT1, TP53, TNF, IL6, MAPK1). Among them, quercetin exhibited the strongest binding affinity with AKT1. RT-qPCR validation in clinical DFU tissue samples demonstrated consistent expression trends with computational predictions: AKT1 was significantly upregulated, while TP53, TNF, IL6, and MAPK1 were markedly downregulated in the Fespixon-treated group compared to controls (p < 0.001), supporting the proposed multi-target therapeutic mechanism. Conclusions: Our study reveals the potential mechanisms by which Fespixon cream exerts therapeutic effects on DFUs. The efficacy of Fespixon cream in treating DFUs is attributed to the synergistic actions of its bioactive components through multiple targets and multiple signaling pathways. Full article

(This article belongs to the Section Molecular Pharmacology)

► Show Figures

Figure 1

20 pages, 2730 KiB

Open AccessArticle

Physiological and Biochemical Responses and Transcriptome Analysis of Bangia fuscopurpurea (Rhodophyta) Under High-Temperature Stress

by Minghao Zhao, Hongyan Zheng, Zepan Chen and Weizhou Chen

Curr. Issues Mol. Biol. 2025, 47(7), 484; https://doi.org/10.3390/cimb47070484 (registering DOI) - 25 Jun 2025

Abstract

With the advancement of human industrial activities, increased carbon dioxide emissions have made global warming an inescapable trend. Elevated temperatures exert profound effects on the viability of large macroalgae. Bangia fuscopurpurea (Rhodophyta) is a commercially important large red alga widely cultivated along the [...] Read more.

With the advancement of human industrial activities, increased carbon dioxide emissions have made global warming an inescapable trend. Elevated temperatures exert profound effects on the viability of large macroalgae. Bangia fuscopurpurea (Rhodophyta) is a commercially important large red alga widely cultivated along the coastal waters of Putian, Fujian Province, China; however, its physiological, biochemical, and molecular responses to heat stress remain unclear. To address this question, we cultured B. fuscopurpurea at 15 °C (control) and 28 °C (heat stress) for 7 days, assessed changes in growth and photosynthetic parameters, and performed transcriptome sequencing. Growth analysis revealed that the relative growth rate of B. fuscopurpurea at 28 °C was significantly lower than that at 15 °C. After 1 day at 28 °C, the chlorophyll a and carotenoid contents increased significantly; the phycobiliprotein levels rose markedly on days 4 and 7, whereas the Fv/Fm ratio decreased significantly on days 1, 4, and 7. Transcriptomic analysis indicated that heat stress up-regulated the majority of differentially expressed genes (DEGs) in B. fuscopurpurea. KEGG pathway enrichment analysis revealed that the DEGs were predominantly associated with photosynthesis, carbohydrate and energy metabolism, glycerophospholipid metabolism, and the glutathione cycle. In summary, B. fuscopurpurea mitigates the adverse effects of heat stress by up-regulating genes involved in photosynthesis, antioxidant defenses, and glycerophospholipid metabolism. These findings enhance our understanding of the physiological adaptations and molecular mechanisms by which B. fuscopurpurea responds to heat stress. Full article

(This article belongs to the Special Issue Molecular Mechanisms in Plant Stress Tolerance)

► Show Figures

Figure 1

20 pages, 617 KiB

Open AccessReview

The Impact of Arsenic, Cadmium, Lead, Mercury, and Thallium Exposure on the Cardiovascular System and Oxidative Mechanisms in Children

by Marcin Wróblewski, Justyna Miłek, Antoni Godlewski and Joanna Wróblewska

Curr. Issues Mol. Biol. 2025, 47(7), 483; https://doi.org/10.3390/cimb47070483 (registering DOI) - 25 Jun 2025

Abstract

Environmental exposure to heavy metals seriously threatens children’s health, potentially impacting the cardiovascular system. Mechanisms such as oxidative stress, inflammation, and lipid metabolism disturbances play a significant role in this process. Although cardiovascular diseases typically manifest in adulthood, an increasing number of studies [...] Read more.

Environmental exposure to heavy metals seriously threatens children’s health, potentially impacting the cardiovascular system. Mechanisms such as oxidative stress, inflammation, and lipid metabolism disturbances play a significant role in this process. Although cardiovascular diseases typically manifest in adulthood, an increasing number of studies suggest that their origins trace back to childhood and result from long-term pathophysiological changes. Therefore, early identification of modifiable risk factors is crucial for effective preventive measures and reducing future health risks. Full article

(This article belongs to the Special Issue Effects of Environmental Factors on Cardiovascular Disease: From Molecular Effects to Possible Future Clinic Application)

► Show Figures

Figure 1

16 pages, 4250 KiB

Open AccessArticle

TNF-α Promotes the Recovery of Dorsal Root Ganglion Neurons from Cisplatin-Induced Injury Through an NGF-Independent Mechanism

by Yiling Wei, Xianlin Xu, Pan Wu, Xiang Chen, Qingmei Mo and Ming Zhuo

Curr. Issues Mol. Biol. 2025, 47(7), 482; https://doi.org/10.3390/cimb47070482 - 24 Jun 2025

Abstract

Nerve injury caused by chemotherapy drugs is a common side effect. How to reduce this kind of nerve injury and promote neuron recovery is of great significance. In this study, we found that tumor necrosis factor-α (TNF-α) promoted the recovery of dorsal root [...] Read more.

Nerve injury caused by chemotherapy drugs is a common side effect. How to reduce this kind of nerve injury and promote neuron recovery is of great significance. In this study, we found that tumor necrosis factor-α (TNF-α) promoted the recovery of dorsal root ganglion (DRG) neuron from cisplatin-induced injury. On DRG neurons cultured in vitro, we found that TNF-α promoted neurite regeneration after cisplatin injury. In addition, TNF-α accelerated the removal of DNA damage and promoted the regeneration of mitochondria on DRG neurons. Study of the mechanism showed that this effect of TNF-α was independent from the NGF signaling pathway and occurred mostly through the activation of TNFR2 receptors, together with nucleus translocation of p65 and upregulation of NF-κB expression. This study provides a new theoretical basis and therapeutic strategy for the treatment of nerve injury caused by chemotherapy drugs. Full article

(This article belongs to the Section Molecular Medicine)

► Show Figures

Figure 1

15 pages, 3444 KiB

Open AccessArticle

Metabolomics and Transcriptome Analysis of Rapeseed Under Salt Stress at Germination Stage

by Menglin Zhou, Xi Song, Qingqing Yu, Bingbing Dai, Wei Zhou, Xiaofei Zan and Wuming Deng

Curr. Issues Mol. Biol. 2025, 47(7), 481; https://doi.org/10.3390/cimb47070481 - 24 Jun 2025

Abstract

Salt stress is a significant abiotic factor that adversely impacts the yield of rapeseed (Brassica napus L.). Under salt stress conditions, the growth of rapeseed is markedly inhibited. This study integrates transcriptomic and metabolomic analyses to elucidate the molecular and physiological mechanisms [...] Read more.

Salt stress is a significant abiotic factor that adversely impacts the yield of rapeseed (Brassica napus L.). Under salt stress conditions, the growth of rapeseed is markedly inhibited. This study integrates transcriptomic and metabolomic analyses to elucidate the molecular and physiological mechanisms underlying the salt stress response during the germination of the rapeseed variety ZS11. Metabolomic analysis revealed 175 differentially expressed metabolites, predominantly comprising amino acids, carbohydrates, and organic acids. Transcriptomic analysis highlighted the crucial roles of plant hormones and phenylpropanoid biosynthesis in enhancing the salt stress resistance of rapeseed. Comprehensive multi-omics analysis identified phenylpropanoid metabolism (p < 0.001), amino acid metabolism (FDR < 0.01), and carbohydrate metabolism (|log₂FC| ≥ 2) as the most significantly affected pathways. Crucially, we demonstrate that early-stage phenylpropanoid activation in hypocotyls dominates salt adaptation during germination. These findings provide actionable targets for molecular breeding and novel insights for optimizing crop establishment in salinized agroecosystems. Full article

(This article belongs to the Special Issue Advances in Multi-Omics for Functional Genomics Studies and Molecular Breeding)

► Show Figures

Figure 1

3 pages, 150 KiB

Open AccessEditorial

Editorial for Special Issue “Molecular Insights into Food-Derived Natural Products and Their Biological Activities”

by Yanfang Li

Curr. Issues Mol. Biol. 2025, 47(7), 480; https://doi.org/10.3390/cimb47070480 - 21 Jun 2025

Abstract

Food-derived natural products offer more than just essential nutrients like vitamins, calcium, iron, zinc, selenium, and so on [...] Full article

(This article belongs to the Special Issue Molecular Insights into Food-Derived Natural Products and Their Biological Activities)

32 pages, 1766 KiB

Open AccessArticle

Peripheral Blood Exosomal miR-184-3p in Methamphetamine Use Disorder: Biomarker Potential and CRTC1-Mediated Neuroadaptation

by Yan Zhao, Zhuoming Zhao, Qianqian Sun, Hang Su, Tianzhen Chen, Xiaomin Xu, Xiaotong Li, Sai Shi, Jiang Du, Haifeng Jiang and Min Zhao

Curr. Issues Mol. Biol. 2025, 47(7), 479; https://doi.org/10.3390/cimb47070479 - 20 Jun 2025

Abstract

The neurobiological mechanisms underlying methamphetamine use disorder (MUD) remain elusive, and specific treatment modalities as well as diagnostic markers are scarce. The emergence of exosomes has opened up possibilities for developing diagnostic and assessment biomarkers for neuropsychiatric disorders. Hence, the present study aimed [...] Read more.

The neurobiological mechanisms underlying methamphetamine use disorder (MUD) remain elusive, and specific treatment modalities as well as diagnostic markers are scarce. The emergence of exosomes has opened up possibilities for developing diagnostic and assessment biomarkers for neuropsychiatric disorders. Hence, the present study aimed to preliminarily explore the alterations in exosomal miRNA expression in MUD patients and the potential mechanisms involved in MUD. First, miRNA sequencing and RT-qPCR were used to verify the differential expression of peripheral blood exosomal miR-184-3p and miR-4433a-5p in MUD patients. Subsequently, the diagnostic ability of these two miRNAs for MUD was evaluated using ROC analysis. Finally, the regulatory relationship between miRNA-184-3p and its downstream target gene CRTC1 was verified by dual luciferase reporter assay. The results demonstrated that exosomal miR-184-3p and miR-4433a-5p were markedly decreased in MUD patients. However, the expression level of miR-4433a-5p was influenced by anxiety-depressive symptoms. The ROC analysis revealed that the AUCs of exosomal miRNA-184-3p in the training and validation sets of MUD patients were 0.902 and 0.823, respectively. In conclusion, exosomal miR-184-3p levels in peripheral blood may be a potential biomarker for the diagnosis and assessment of MUD, and it may be involved in the pathophysiological process of MUD through the targeted regulation of the CRTC1/CREB pathway. Full article

(This article belongs to the Special Issue Mental Disorder: Focus on Pathogenesis to Treatment)

15 pages, 6351 KiB

Open AccessArticle

IGFBP2 Modulates Trophoblast Function and Epithelial–Mesenchymal Transition in Preeclampsia via the PI3K/AKT Signaling Pathway

by Shengping Meng, Yanping Qin, Chunyan Lyu and Sumei Wang

Curr. Issues Mol. Biol. 2025, 47(7), 478; https://doi.org/10.3390/cimb47070478 - 20 Jun 2025

Abstract

Background: Preeclampsia (PE) is a deadly obstetric complication in pregnant women leading to escalated rates of maternal and fetal mortality. Current research indicates that inadequate invasion of extravillous trophoblasts (EVTs) is a primary factor associated with the pathogenesis of PE. Insulin-like growth factor [...] Read more.

Background: Preeclampsia (PE) is a deadly obstetric complication in pregnant women leading to escalated rates of maternal and fetal mortality. Current research indicates that inadequate invasion of extravillous trophoblasts (EVTs) is a primary factor associated with the pathogenesis of PE. Insulin-like growth factor binding protein 2 (IGFBP2) plays a significant role in promoting cell migration, invasion, and angiogenesis. Researchers aim to investigate the clinical significance and elucidate the molecular mechanisms of IGFBP2 in the pathogenesis of preeclampsia. Methods: This study included 40 pregnant women categorized into 20 PE patients and 20 healthy controls. Expression levels of the mRNA were quantified using real-time quantitative polymerase chain reaction (qRT-PCR), and protein levels were assessed through Western blotting and immunofluorescence techniques. Moreover, the gain- and loss-of-function assays were conducted in human trophoblast cell line HTR-8/SVneo, and cellular models exhibiting overexpression and the knockdown of IGFBP2 were established. The proliferation, migration, and invasion of HTR-8/Svneo cells were determined using CCK8, wound-healing, and transwell assays, respectively. Results: The IGFBP2 was significantly downregulated, and the EMT was suppressed in the placental tissues of the PE patients. Functional experiments demonstrated that IGFBP2 enhanced the proliferation, invasion, and EMT of trophoblast cells activated through the PI3K/AKT signaling pathway. Conclusion: Our findings indicated that IGFBP2 enhances the proliferation, invasion, and EMT of trophoblast cells by activating the PI3K/AKT signaling pathway, serving as a potential therapeutic target in PE patients. Full article

(This article belongs to the Special Issue Advanced Molecular Research on Hypertensive Disorders of Pregnancy (HDPs))

► Show Figures

Graphical abstract

24 pages, 2227 KiB

Open AccessReview

An Insight into Cancer Cells and Disease Progression Through the Lens of Mathematical Modeling

by Polychronis Michalakis, Dimitra Vasilaki, Ali Jihad Abdallah, Charilaos Asikis, Athina Niakou, Athanasios Stratos, Alexandros Tsouknidas, Elaine Johnstone and Konstantinos Michalakis

Curr. Issues Mol. Biol. 2025, 47(7), 477; https://doi.org/10.3390/cimb47070477 - 20 Jun 2025

Abstract

During cancer initiation, normal cells acquire mutations disrupting standard cellular processes, activating oncogenes and inactivating tumor suppressor genes, acquiring the well-described hallmarks of cancer on the path to malignancy. This process is influenced by a combination of physiological and metabolic pathways, as well [...] Read more.

During cancer initiation, normal cells acquire mutations disrupting standard cellular processes, activating oncogenes and inactivating tumor suppressor genes, acquiring the well-described hallmarks of cancer on the path to malignancy. This process is influenced by a combination of physiological and metabolic pathways, as well as environmental cues, and leads to abnormal cell cycle, increased cell motility, and invasive characteristics. Cancer cell organelles also present some distinct differences from those of normal cells. Cancer progression requires certain tumorigenic biochemical pathways to be activated. However, mechanical cues are also important, as they have an effect on cell differentiation and fate. A continuous biochemical–biomechanical interaction exists, which affects the mechanical properties of the cells, as well as their behavior. This review aims to focus on the mathematical relationships governing cancer mechanobiology and examine how the altered mechanical properties of a cancer cell may affect malignant progression. Full article

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

► Show Figures

Figure 1

16 pages, 5066 KiB

Open AccessArticle

Mitochondrial Genomes of Four Millipedes (Diplopoda: Spirostreptida and Spirobolida) Unveil Phylogenetic Novelty and Gene Rearrangement Patterns

by Yingzhu Li, Gaoji Zhang, Wei Xu, Tangjun Xu, Lingna Li, Ming Gao, Jiachen Wang and Hongyi Liu

Curr. Issues Mol. Biol. 2025, 47(6), 476; https://doi.org/10.3390/cimb47060476 - 19 Jun 2025

Abstract

Millipedes (Diplopoda) are crucial decomposers in soil ecosystems, as they play a vital role in organic matter degradation while also holding potential as bioindicators of environmental health. This study deciphered the complete mitogenomes of four millipede species (Diplopoda: Spirostreptida and Spirobolida) using next-generation [...] Read more.

Millipedes (Diplopoda) are crucial decomposers in soil ecosystems, as they play a vital role in organic matter degradation while also holding potential as bioindicators of environmental health. This study deciphered the complete mitogenomes of four millipede species (Diplopoda: Spirostreptida and Spirobolida) using next-generation sequencing technology, thus revealing evolutionary relationships among diplopod taxa and characterizing mitochondrial genomic features. The full mitochondrial sequences of Agaricogonopus acrotrifoliolatus, Bilingulus sinicus, Paraspirobolus lucifugus, and Trigoniulus corallinus, ranged in size from 14,906 to 15,879 bp, with each containing 37 typical genes and one D-loop region. Notably, the D-loop regions of A. acrotrifoliolatus and B. sinicus were positioned atypically, thus indicating structural rearrangements. A nucleotide composition analysis revealed pronounced AT-skews, with tRNA sequences exhibiting the highest A+T content. Ka/Ks ratios demonstrated that the ND5 gene experienced the weakest purifying selection pressure, thus suggesting its potential role in adaptive evolution. The results of the phylogenetic analysis showed genetic relationships between the three orders of ((Julida, Spirostreptida), Spirobolida), which was inconsistent with the previous conclusion regarding the three orders, obtained through morphological studies: ((Julida, Spirobolida), Spirostreptida). These findings highlight the role of the mitochondrial genome in resolving phylogenetic conflicts and provide important insights for further studies on millipedes. Full article

(This article belongs to the Special Issue Mitochondrial Genomes 2025: Unraveling the Threads of Evolution and Function)

► Show Figures

Figure 1

47 pages, 986 KiB

Open AccessReview

Integrating Genomics and Molecular Biology in Understanding Peritoneal Adhesion

by Mirela Lungu, Claudiu N. Lungu, Andreea Creteanu and Mihaela C. Mehedinti

Curr. Issues Mol. Biol. 2025, 47(6), 475; https://doi.org/10.3390/cimb47060475 - 19 Jun 2025

Abstract

Peritoneal adhesions following surgical injury remain a major clinical challenge, often resulting in severe complications, such as intestinal obstruction, chronic pain, and infertility. This review systematically integrates recent genomic and molecular biology insights into the pathogenesis of peritoneal adhesions, explicitly focusing on molecular [...] Read more.

Peritoneal adhesions following surgical injury remain a major clinical challenge, often resulting in severe complications, such as intestinal obstruction, chronic pain, and infertility. This review systematically integrates recent genomic and molecular biology insights into the pathogenesis of peritoneal adhesions, explicitly focusing on molecular pathways, including TGF-β signaling, COX-2-mediated inflammatory responses, fibrinolytic balance (tPA/PAI-1), angiogenesis pathways (VEGF, PDGF), and extracellular matrix remodeling (MMPs/TIMPs). Newly conducted transcriptomic and proteomic analyses highlight distinct changes in gene expression patterns in peritoneal fibroblasts during adhesion formation, pinpointing critical roles for integrins, cadherins, selectins, and immunoglobulin superfamily molecules. Recent studies indicate significant shifts in TGF-β isoforms expression, emphasizing isoform-specific impacts on fibrosis and scarring. These insights reveal substantial knowledge gaps, particularly the differential regulatory mechanisms involved in fibrosis versus normal reparative reperitonealization. Future therapeutic strategies could target these molecular pathways and inflammatory mediators to prevent or reduce adhesion formation. Further research into precise genetic markers and the exploration of targeted pharmacological interventions remain pivotal next steps in mitigating postoperative adhesion formation and improving clinical outcomes. Full article

(This article belongs to the Special Issue Molecular Keys to Bioactivity: Pharmacophore and SAR Exploration in Organic Compounds)

► Show Figures

Figure 1

14 pages, 3426 KiB

Open AccessArticle

L-Ascorbic Acid (LAA) Supplementation as a Potential Treatment for Skin Aging: Regulation of Adipose Tissue Mesenchymal Stem Cells (AT-MSCs) Protein Secretion

by Komang Ardi Wahyuningsih, I. Gede Eka Wiratnaya, I. Wayan Weta, I. Gde Raka Widiana, Wimpie I. Pangkahila, Ida Ayu Ika Wahyuniari, I. Made Muliarta, Veronika Maria Sidharta and Assyafiya Salwa

Curr. Issues Mol. Biol. 2025, 47(6), 474; https://doi.org/10.3390/cimb47060474 - 19 Jun 2025

Abstract

Skin aging is mostly caused by the accumulation of reactive oxygen species (ROS) that lead to cellular dysfunction. One promising therapy for skin aging is the secretome product of adipose tissue mesenchymal stem cells (AT-MSCs). L-ascorbic acid (LAA) is an essential molecule for [...] Read more.

Skin aging is mostly caused by the accumulation of reactive oxygen species (ROS) that lead to cellular dysfunction. One promising therapy for skin aging is the secretome product of adipose tissue mesenchymal stem cells (AT-MSCs). L-ascorbic acid (LAA) is an essential molecule for preventing oxidative stress as an external antioxidant agent and has been used in chemical therapy for skin aging. In this study, we evaluated the effects of LAA on cell morphology, the number of cells, cell viability, and the paracrine secretion of preconditioned AT-MSCs in in vitro culture with LAA in 100 and 200 µg/mL compared with an untreated culture with LAA as a control. LAA supplementation in both concentrations improved the morphology of cells without affecting the cell viability. However, there was no significant improvement in the number of cells even though the trend showed an enhancement of the number of cells. The total protein of the secretome decreased in the LAA preconditioning group. However, preconditioning AT-MSCs in in vitro culture with LAA improved the levels of insulin-like growth factor 1 (IGF-1), transforming growth factor β1 (TGF-β1), and interleukin 6 (IL-6) which are essential proteins for skin aging in regulating ROS. Full article

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

► Show Figures

Graphical abstract

12 pages, 1531 KiB

Open AccessArticle

Association of DROSHA Variants with Susceptibility and Outcomes in Childhood Acute Lymphoblastic Leukemia

by Ioannis Kyriakidis, Iordanis Pelagiadis, Charalampos Pontikoglou, Helen A. Papadaki and Eftichia Stiakaki

Curr. Issues Mol. Biol. 2025, 47(6), 473; https://doi.org/10.3390/cimb47060473 - 19 Jun 2025

Abstract

MicroRNAs are key regulators of lymphoid differentiation, exhibiting a pivotal role in acute lymphoblastic leukemia (ALL) biology and prognosis. The initial steps of canonical miRNA biogenesis involve the microprocessor complex processing the primary miRNA transcripts into precursor miRNAs via Drosha. DROSHA polymorphisms have [...] Read more.

MicroRNAs are key regulators of lymphoid differentiation, exhibiting a pivotal role in acute lymphoblastic leukemia (ALL) biology and prognosis. The initial steps of canonical miRNA biogenesis involve the microprocessor complex processing the primary miRNA transcripts into precursor miRNAs via Drosha. DROSHA polymorphisms have been implicated in pediatric ALL and linked with cancer risk. This study investigated the role of rs642321, rs3805500, and rs10035440 DROSHA polymorphisms in ALL susceptibility, relapse, and outcomes in children and adolescents of Greek descent. The study included 252 children and adolescents (115 ALL cases and 137 controls). Genotyping was performed using RT-qPCR and the TaqMan Genotyping Assay. Homozygotes for the minor allele in DROSHA rs642321 were nominally associated with ALL susceptibility (TT vs. CC+CT; OR 4.5; 95% CI: 1.2–21.2; p_adj = 0.034). Likewise, homozygotes for the minor allele in rs3805500 were linked with ALL risk (GG vs. AA+AG; OR 2.7; 95% CI: 1.3–6.1; p_adj = 0.012). A suggestive association was observed between the rs3805500 AG genotype and both relapsed (OR 5.8; 95% CI: 1.6–24.3; p_adj = 0.011) and deceased cases (OR 5; 95% CI: 1.1–26.3; p_adj = 0.038). Patients with the rs3805500 AG and GG genotypes showed a trend toward poorer overall survival rates. In summary, certain haplotypes of DROSHA polymorphisms may be modestly associated with the occurrence of childhood ALL and its outcomes, although these findings require validation in larger, independent cohorts. Full article

(This article belongs to the Special Issue Genomic Analysis of Common Disease, 2nd Edition)

► Show Figures

Figure 1

22 pages, 389 KiB

Open AccessReview

Copper Nanoparticles in Aquatic Environment: Release Routes and Oxidative Stress-Mediated Mechanisms of Toxicity to Fish in Various Life Stages and Future Risks

by Anna Sielska and Lidia Skuza

Curr. Issues Mol. Biol. 2025, 47(6), 472; https://doi.org/10.3390/cimb47060472 - 19 Jun 2025

Abstract

The final recipient of nanoparticles, including various types of copper-based nanoparticles (Cu-based NPs), is the aquatic environment. Their increased production, especially as a component of antimicrobial agents, raises concerns about uncontrolled environmental release and subsequent ecological risks. The high reactivity of Cu-based NPs [...] Read more.

The final recipient of nanoparticles, including various types of copper-based nanoparticles (Cu-based NPs), is the aquatic environment. Their increased production, especially as a component of antimicrobial agents, raises concerns about uncontrolled environmental release and subsequent ecological risks. The high reactivity of Cu-based NPs enables interactions with biotic and abiotic environmental components, leading to bioaccumulation and disorders in living organisms, such as fish in various life stages, especially in embryos or hatchlings. Increasing concentration of Cu-based NPs causes various toxic effects, mainly through the induction of oxidative stress. These effects include impairment of antioxidant mechanisms, as well as damage to genetic material, cells and tissues, growth retardation, metabolic disorders, increased mortality, or hatching inhibition. The aim of this review is to describe the release routes of Cu-based NPs and their adverse effects on fish, while emphasizing the need for further research on their toxicity and measures to control their release to the environment. Given the limited data on the toxicity of Cu-based NPs, especially concerning sensitive fish developmental stages, further studies are required. Full article

(This article belongs to the Special Issue Innovations in Marine Biotechnology and Molecular Biology)

19 pages, 3071 KiB

Open AccessReview

The Known Unknowns: An Enigmatic Pathway of C₁₇-Polyacetylenic Oxylipins in Carrot (Daucus carota L.)

by Abdul Wakeel Umar, Hamad Hussain and Naveed Ahmad

Curr. Issues Mol. Biol. 2025, 47(6), 471; https://doi.org/10.3390/cimb47060471 - 19 Jun 2025

Abstract

C₁₇-polyacetylenic (PA) oxylipins are bioactive compounds in carrots (Daucus carota L.) with structurally unique features and diverse biological roles. These PA-derived compounds have garnered attention for their potential contributions to human health, particularly in cancer prevention and anti-inflammatory applications. This [...] Read more.

C₁₇-polyacetylenic (PA) oxylipins are bioactive compounds in carrots (Daucus carota L.) with structurally unique features and diverse biological roles. These PA-derived compounds have garnered attention for their potential contributions to human health, particularly in cancer prevention and anti-inflammatory applications. This trade-off between health benefits and sensory quality underscores the importance of understanding the genetic and biochemical basis of PA biosynthesis, as it may allow for the development of carrots with optimized levels of these compounds that balance both nutritional and sensory qualities. In this review, we seek biochemically inspired strategies to elucidate the complexities of PA-derived oxylipins biosynthesis in carrots, a topic that remains largely unexplored. By integrating current knowledge on polyacetylene biology, biosynthesis, genetic and enzymatic factors involved in their production and the implications for enhancing the medicinal value of carrots we aim to provide a foundation for future research that could unlock the full potential of carrots as a source of health-promoting bioactive compounds. Full article

(This article belongs to the Special Issue Molecular Mechanism of Plant Growth, Development and Secondary Metabolism)

► Show Figures

Figure 1

26 pages, 916 KiB

Open AccessReview

Integrating Artificial Intelligence in Next-Generation Sequencing: Advances, Challenges, and Future Directions

by Konstantina Athanasopoulou, Vasiliki-Ioanna Michalopoulou, Andreas Scorilas and Panagiotis G. Adamopoulos

Curr. Issues Mol. Biol. 2025, 47(6), 470; https://doi.org/10.3390/cimb47060470 - 19 Jun 2025

Abstract

The integration of artificial intelligence (AI) into next-generation sequencing (NGS) has revolutionized genomics, offering unprecedented advancements in data analysis, accuracy, and scalability. This review explores the synergistic relationship between AI and NGS, highlighting its transformative impact across genomic research and clinical applications. AI-driven [...] Read more.

The integration of artificial intelligence (AI) into next-generation sequencing (NGS) has revolutionized genomics, offering unprecedented advancements in data analysis, accuracy, and scalability. This review explores the synergistic relationship between AI and NGS, highlighting its transformative impact across genomic research and clinical applications. AI-driven tools, including machine learning and deep learning, enhance every aspect of NGS workflows—from experimental design and wet-lab automation to bioinformatics analysis of the generated raw data. Key applications of AI integration in NGS include variant calling, epigenomic profiling, transcriptomics, and single-cell sequencing, where AI models such as CNNs, RNNs, and hybrid architectures outperform traditional methods. In cancer research, AI enables precise tumor subtyping, biomarker discovery, and personalized therapy prediction, while in drug discovery, it accelerates target identification and repurposing. Despite these advancements, challenges persist, including data heterogeneity, model interpretability, and ethical concerns. This review also discusses the emerging role of AI in third-generation sequencing (TGS), addressing long-read-specific challenges, like fast and accurate basecalling, as well as epigenetic modification detection. Future directions should focus on implementing federated learning to address data privacy, advancing interpretable AI to improve clinical trust and developing unified frameworks for seamless integration of multi-modal omics data. By fostering interdisciplinary collaboration, AI promises to unlock new frontiers in precision medicine, making genomic insights more actionable and scalable. Full article

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

► Show Figures

Graphical abstract

16 pages, 3913 KiB

Open AccessArticle

Isolation and Characterization of Enterococcus faecalis Phage ZXL-01 and Preliminary Investigation of Its Therapeutic Effect on Periapical Periodontitis

by Hailin Jiang, Xueli Zhao, Chuhan Wang, Hongyan Shi, Jinghua Li, Chunyan Zhao and Honglan Huang

Curr. Issues Mol. Biol. 2025, 47(6), 469; https://doi.org/10.3390/cimb47060469 - 18 Jun 2025

Abstract

Enterococcus faecalis (E. faecalis) is a major pathogen responsible for refractory apical periodontitis (RAP). It can penetrate deep into dentinal tubules, form persistent biofilms, and exhibit antibiotic resistance, thereby limiting the efficacy of conventional antimicrobial treatments. Bacteriophages (phages), due to their [...] Read more.

Enterococcus faecalis (E. faecalis) is a major pathogen responsible for refractory apical periodontitis (RAP). It can penetrate deep into dentinal tubules, form persistent biofilms, and exhibit antibiotic resistance, thereby limiting the efficacy of conventional antimicrobial treatments. Bacteriophages (phages), due to their strong lytic activity and host specificity, have emerged as promising alternatives. In this study, a novel strictly lytic phage, ZXL-01, was isolated from lake water in Jilin, China. ZXL-01 demonstrated remarkable stability under extreme conditions, including thermal tolerance at 60 °C for 1 h and a wide pH range (4–11). Whole-genome sequencing (GenBank accession number: ON113334) revealed a genome of 40,804 bp with no virulence or tRNA genes, confirming its identity as an E. faecalis phage. Importantly, ZXL-01 exhibited potent antibiofilm activity, reducing biofilm biomass by approximately 69.4% in the inhibition group and 68.4% in the lysis group (both p < 0.001). In an in vitro root canal infection model induced by E. faecalis, scanning electron microscope (SEM) observations confirmed that ZXL-01 effectively inhibited biofilm formation and disrupted mature biofilms. These findings highlight the potential of ZXL-01 as a novel antimicrobial agent for the treatment of E. faecalis-associated apical periodontitis. Full article

(This article belongs to the Section Molecular Microbiology)

► Show Figures

Figure 1

Journal Description

Current Issues in Molecular Biology

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI