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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 17.8 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 2025).
Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names are published annually in the journal.

Impact Factor: 3.0 (2024); 5-Year Impact Factor: 3.2 (2024)

Imprint Information Journal Flyer Open Access ISSN: 1467-3045

Latest Articles

10 pages, 900 KiB

Open AccessBrief Report

The Isoforms of Ral Guanine Nucleotide Dissociation Stimulator (RalGDS) in LLC-PK1 Cells

by Jingze Song, Na Li, Xinze Dong, Jianping Xie, Hongqiao Lai, Hengzhi Zhu, Kongwang He, Libin Wen, Sizhu Suolang and Qi Xiao

Curr. Issues Mol. Biol. 2025, 47(7), 566; https://doi.org/10.3390/cimb47070566 - 18 Jul 2025

This study investigated the isoforms of porcine-origin Ral guanine nucleotide dissociation stimulator (RalGDS) in LLC-PK1 cells using reverse transcription-polymerase chain reaction (RT-PCR) and sequencing. Through segmented amplification, sequence assembly, and comparative genomics analysis, seven RalGDS isoforms were identified, characterized by insertions, deletions, and [...] Read more.

This study investigated the isoforms of porcine-origin Ral guanine nucleotide dissociation stimulator (RalGDS) in LLC-PK1 cells using reverse transcription-polymerase chain reaction (RT-PCR) and sequencing. Through segmented amplification, sequence assembly, and comparative genomics analysis, seven RalGDS isoforms were identified, characterized by insertions, deletions, and frameshift mutations. These genetic variations may significantly alter RalGDS’s protein structure and function, potentially impacting its role in Ral GTPase-mediated signaling pathways. This work provides foundational insights into the genetic diversity of porcine RalGDS and its implications for porcine physiology and economically significant traits. Full article

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

25 pages, 1538 KiB

Open AccessReview

Lipid Hormones at the Intersection of Metabolic Imbalances and Endocrine Disorders

by Maria-Zinaida Dobre, Bogdana Virgolici and Ruxandra Cioarcă-Nedelcu

Curr. Issues Mol. Biol. 2025, 47(7), 565; https://doi.org/10.3390/cimb47070565 - 18 Jul 2025

Lipid hormone imbalances involving glucocorticoids, thyroid hormones (THs), and sex hormones have widespread metabolic consequences, contributing to the global increase in obesity and insulin resistance. This review examines the complex role of disrupted lipid hormone pathways in the development of metabolic disorders, particularly [...] Read more.

Lipid hormone imbalances involving glucocorticoids, thyroid hormones (THs), and sex hormones have widespread metabolic consequences, contributing to the global increase in obesity and insulin resistance. This review examines the complex role of disrupted lipid hormone pathways in the development of metabolic disorders, particularly metabolic dysfunction-associated steatotic liver disease (MASLD). Endocrine disorders such as hypercortisolism, hypothyroidism, and polycystic ovary syndrome (PCOS) are closely linked to MASLD through shared metabolic pathways. Mechanisms include glucocorticoid-induced gluconeogenesis and lipolysis, impaired lipid clearance in hypothyroidism, and the hyperandrogenism-induced downregulation of hepatic low-density lipoprotein (LDL) receptors. PCOS-related factors—such as central obesity, adipocyte hypertrophy, low adiponectin levels, and genetic predisposition—further promote hepatic steatosis. Thyroid dysfunction may also impair the hepatic deiodination of T4, contributing to lipid accumulation and inflammation. Given the overlapping pathophysiology among endocrine, hepatic, and reproductive disorders, multidisciplinary collaboration is essential to optimize diagnosis, treatment, and long-term cardiometabolic outcomes. Full article

(This article belongs to the Special Issue Molecular Mechanisms Underlying Fatty Liver Disease: From Pathogenesis to Treatment, 2nd Edition)

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10 pages, 1286 KiB

Open AccessCommunication

Establishment of an Assay with Ultrahigh Sensitivity for Detecting sEV-Derived PD-L1 as a Serum Biomarker for Lung Cancer—A Pilot Study Using TN-cyclon™

by Kyo Okita, Hasumi Arita, Keita Sudo, Teruki Yoshimura and Etsuro Ito

Curr. Issues Mol. Biol. 2025, 47(7), 564; https://doi.org/10.3390/cimb47070564 - 18 Jul 2025

Programmed death-ligand 1 (PD-L1) is an immune checkpoint protein. The soluble form of PD-L1 (sPD-L1) and PD-L1 derived from small extracellular vesicles (sEVPD-L1) are promising cancer biomarkers. While sEVPD-L1 in particular may contribute to immune evasion and is associated with a poor prognosis, [...] Read more.

Programmed death-ligand 1 (PD-L1) is an immune checkpoint protein. The soluble form of PD-L1 (sPD-L1) and PD-L1 derived from small extracellular vesicles (sEVPD-L1) are promising cancer biomarkers. While sEVPD-L1 in particular may contribute to immune evasion and is associated with a poor prognosis, it exists only in trace amounts, making it difficult to detect using conventional enzyme-linked immunosorbent assay (ELISA) methods. Therefore, we developed an ultrasensitive detection method, TN-cyclon™. The TN-cyclon™ method combines sandwich ELISA with enzyme cycling amplification. We applied TN-cyclon™ to measure recombinant PD-L1 protein and sEVPD-L1 in serum samples from cancer patients and healthy donors. Recombinant PD-L1 protein was measured with an ultrasensitive detection limit of 0.172 pg/mL. In clinical specimens, sEVPD-L1 levels were significantly higher in lung cancer patients than in healthy donors, whereas sPD-L1 levels measured with a conventional ELISA did not differ significantly between groups. Our results demonstrated that the TN-cyclon™ method exhibits a 20-fold increase in sensitivity compared to a conventional ELISA. Although this is a pilot study, our new assay enables the detection of very low concentrations of sEVPD-L1 in serum that can be used to evaluate the predictive and prognostic performance of sEVPD-L1 in lung cancer patients in future studies. Full article

(This article belongs to the Special Issue Cancer Biomarkers: Discovery and Applications)

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16 pages, 4588 KiB

Open AccessArticle

CTC-537E7.3 as a Liver-Specific Biomarker for Hepatocellular Carcinoma: Diagnostic and Prognostic Implications

by Hyung Seok Kim, Se Ha Jang, Geum Ok Baek, Moon Gyeong Yoon, Jaewon Shim, Ji Eun Han, Soon Sun Kim, Jae Youn Cheong and Jung Woo Eun

Curr. Issues Mol. Biol. 2025, 47(7), 563; https://doi.org/10.3390/cimb47070563 - 18 Jul 2025

Hepatocellular carcinoma (HCC) critically lacks reliable biomarkers for early detection. By mining the TCGA_LIHC and two GEO cohorts, we identified the liver-specific long non-coding RNA CTC-537E7.3 as the most consistently down-regulated transcript in tumors. This finding was validated in 97 paired tissues, with [...] Read more.

Hepatocellular carcinoma (HCC) critically lacks reliable biomarkers for early detection. By mining the TCGA_LIHC and two GEO cohorts, we identified the liver-specific long non-coding RNA CTC-537E7.3 as the most consistently down-regulated transcript in tumors. This finding was validated in 97 paired tissues, with CTC-537E7.3 expression lost in 95% of cases (*** p < 0.0001). It demonstrated excellent diagnostic performance in discriminating tumor from non-tumor tissue (AUC = 0.95), which was maintained in early-stage (I/II) disease. Low CTC-537E7.3 expression correlated with shorter overall and disease-free survival and was inversely associated with serum α-fetoprotein (AFP) levels, highlighting its complementary clinical value. Mechanistic investigation revealed a potential competing endogenous RNA (ceRNA) axis. The microRNA miR-190b-5p was highly expressed in tumors and predicted to bind CTC-537E7.3, while its target, PLGLB1, was significantly suppressed. Survival analysis confirmed that concurrent high expression of CTC-537E7.3 and PLGLB1 conferred superior outcomes. These findings establish CTC-537E7.3 as a liver-specific, ceRNA-mediated tumor suppressor with robust diagnostic and prognostic potential. It represents a promising adjunct to existing HCC surveillance strategies, such as ultrasound and AFP measurement, for high-risk populations. Full article

(This article belongs to the Special Issue Epigenetic Changes in Cancer: Mechanisms, Biomarkers, and Therapeutic Strategies)

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13 pages, 5701 KiB

Open AccessArticle

High-Fat/High-Sugar Diet and High-Temperature/High-Humidity Exposure Aggravates Ulcerative Colitis in an Experimental Mouse Model

by Pengyan Li, Guibing Meng, Ang Li, Liang Chen, Xinchi Feng and Feng Qiu

Curr. Issues Mol. Biol. 2025, 47(7), 562; https://doi.org/10.3390/cimb47070562 - 18 Jul 2025

Ulcerative colitis (UC) is a subtype of inflammatory bowel disease (IBD) that has been associated with overconsumption of calories and lipids, compared to the healthy population, and summer temperatures have been reported to be closely related to the prevalence of UC. To evaluate [...] Read more.

Ulcerative colitis (UC) is a subtype of inflammatory bowel disease (IBD) that has been associated with overconsumption of calories and lipids, compared to the healthy population, and summer temperatures have been reported to be closely related to the prevalence of UC. To evaluate the effects of dietary and lifestyle factors on UC, a combination of 2.0% dextran sulfate sodium (DSS), a high-fat/high-sugar diet, and exposure to high temperature and humidity was used to construct mouse models of UC. Changes in body weight, disease activity index (DAI) scores, histopathological analysis, serum lipid levels, serum diamine oxidase (DAO), and D-Lactate (D-LA) levels, as well as the expression of inflammatory cytokines and tight junction proteins in colonic tissue, were all assessed to study the impacts of the high-fat/high-sugar diet and high-temperature/high-humidity exposure on the progression of UC. The symptoms observed in the UC mouse model induced by 2.0% DSS alone were similar to those seen in patients with UC, while the high-fat and high-sugar diet, along with humid and hot exposure, exacerbated DSS-induced UC in the mice. This included more severe histopathological damage to the colon tissue, increased expression of pro-inflammatory cytokines (IL-6, IL-17A, and IL-1β), and a more significantly compromised intestinal barrier, characterized by the destruction of ZO-1 and elevated levels of DAO and D-LA. Additionally, the high-fat/high-sugar diet and high-temperature/high-humidity exposure led to further disturbances in glucose and lipid metabolism in the mice, which were not observed in those treated with DSS alone. This study is the first to investigate the effects of a high-fat/high-sugar diet and high-temperature/high-humidity exposure on the progression of UC. Full article

(This article belongs to the Section Molecular Pharmacology)

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14 pages, 594 KiB

Open AccessReview

The Aging Lung: Exploring Multimorbidity Patterns and Their Clinical Implications: A Narrative Review

by Ali Albarrati and Nichola S. Gale

Curr. Issues Mol. Biol. 2025, 47(7), 561; https://doi.org/10.3390/cimb47070561 - 18 Jul 2025

Aging is a multifaceted biological process characterized by a progressive decline in cellular function and physiological resilience, increasing the risk of multiple chronic conditions. Chronic lung diseases frequently manifest within the aging population and are closely intertwined with systemic dysfunctions across cardiovascular, musculoskeletal, [...] Read more.

Aging is a multifaceted biological process characterized by a progressive decline in cellular function and physiological resilience, increasing the risk of multiple chronic conditions. Chronic lung diseases frequently manifest within the aging population and are closely intertwined with systemic dysfunctions across cardiovascular, musculoskeletal, and neurological systems. In this review, we explore the biological mechanisms linking aging, multiple chronic conditions patterns, and chronic lung disease, with a particular focus on inflammaging and cellular aging. We also highlight shared pathological pathways such as oxidative stress, mitochondrial dysfunction, and the dysregulation of repair processes that underlie both natural aging and the accelerated aging seen in chronic lung disease. Additionally, we discuss the systemic impact of multiple chronic conditions on patient outcomes, including increased frailty, diminished physical capacity, cognitive impairment, and elevated mortality risk. This review advocates for a comprehensive, patient-centered approach that combines early detection, personalized pharmacological therapies targeting inflammatory and senescent pathways, and non-pharmacological interventions such as pulmonary rehabilitation, exercise, and dietary optimization. Emerging therapeutics, including senolytics and anti-inflammatory agents, present promising avenues for mitigating age-related lung decline and managing multiple chronic conditions. Full article

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

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11 pages, 1124 KiB

Open AccessArticle

Next-Generation Sequencing Reveals the Potential Role of RET Protooncogene in Metastasis Progression in Medullary Thyroid Cancer

by Maurice Klein, Anna Julia Claudia Klein, Arnold M. Raem, Nicklas Garrelfs, Henrike J. Fischer, Frank Hölzle and Kai Wermker

Curr. Issues Mol. Biol. 2025, 47(7), 560; https://doi.org/10.3390/cimb47070560 - 18 Jul 2025

Background: Medullary thyroid carcinoma (MTC) has a high rate of local and distant metastases. In particular, the RET protooncogene appears to be the predominant driver mutation for oncogenesis. The German S3 thyroid carcinoma guidelines recommend molecular genetic analysis of the tumour without specifying [...] Read more.

Background: Medullary thyroid carcinoma (MTC) has a high rate of local and distant metastases. In particular, the RET protooncogene appears to be the predominant driver mutation for oncogenesis. The German S3 thyroid carcinoma guidelines recommend molecular genetic analysis of the tumour without specifying the site of the tissue sampling. Whether there is difference in RET protooncogene between the primary tumour, lymph node, and distant metastasis has not yet been investigated. However, differences could be important with regard to biopsy localization, and also, thus, the choice of single- or multi-tyrosine-kinase-inhibitor therapy. Methods: In a case of sporadic MTC, Cancer Hotspot panel diagnostics were performed on the primary tumour, lymph node metastasis, and distant metastasis. Mutations were classified using different gene databases, and the different stages of metastasis were compared. Results: RET protooncogene (chr10:43609933, c.1886_1891delTGTGCG, p.Leu629_Asp631delinsHis) was found to be present in the MTC tissue of the primary tumour, lymph node, and distant metastasis in the Cancer Hotspot Panel diagnostic, while the other investigated therapy-relevant mutational profiles were not consistently found. Conclusions: Further longitudinal studies in larger patient cohorts are required to elucidate the role of the RET protooncogene in the metastatic progression of MTC and to determine its impact on the selection of biopsy sites and the subsequent decision-making regarding single- versus multi-tyrosine kinase inhibitor therapy. Full article

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

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34 pages, 1051 KiB

Open AccessReview

Atrial Fibrillation in Diabetes: Pathogenesis and Targeted Rhythm Control Strategies

by Konstantinos Grigoriou, Paschalis Karakasis, Konstantinos Pamporis, Panagiotis Theofilis, Dimitrios Patoulias, Efstratios Karagiannidis, Barbara Fyntanidou, Antonios P. Antoniadis and Nikolaos Fragakis

Curr. Issues Mol. Biol. 2025, 47(7), 559; https://doi.org/10.3390/cimb47070559 - 17 Jul 2025

Diabetes mellitus and atrial fibrillation (AF) frequently coexist, creating a complex bidirectional relationship that exacerbates cardiovascular risk and challenges clinical management. Diabetes fosters a profibrotic, pro-inflammatory, and proarrhythmic atrial substrate through a constellation of pathophysiologic mechanisms, including metabolic remodeling, oxidative stress, mitochondrial dysfunction, [...] Read more.

Diabetes mellitus and atrial fibrillation (AF) frequently coexist, creating a complex bidirectional relationship that exacerbates cardiovascular risk and challenges clinical management. Diabetes fosters a profibrotic, pro-inflammatory, and proarrhythmic atrial substrate through a constellation of pathophysiologic mechanisms, including metabolic remodeling, oxidative stress, mitochondrial dysfunction, ion channel dysregulation, and autonomic imbalance, thereby promoting AF initiation and progression. Conventional rhythm control strategies remain less effective in diabetic individuals, underscoring the need for innovative, substrate-targeted interventions. In this context, sodium–glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as promising agents with pleiotropic antiarrhythmic properties, modulating fibrosis, inflammation, and mitochondrial integrity. Moreover, advances in anti-inflammatory, antifibrotic, and ion channel-modulating therapeutics, coupled with novel mitochondrial-targeted strategies, are reshaping the therapeutic landscape. Multi-omics approaches are further refining our understanding of diabetes-associated AF, facilitating precision medicine and biomarker-guided interventions. This review delineates the molecular nexus linking diabetes and AF, critically appraises emerging rhythm control strategies, and outlines translational avenues poised to advance individualized management in this high-risk population. Full article

(This article belongs to the Special Issue Advances in Molecular Therapies and Disease Associations in Diabetes)

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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

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, 1102 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

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)

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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

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

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

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

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

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

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

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

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

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

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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