Current Issues in Molecular Biology

15 pages, 3990 KB

Open AccessArticle

Application of Raman Spectroscopy to Rapid Discrimination of Autochthonous Lactic Acid Bacteria Isolated from Goat Cheese

by Ana Yanina Bustos, Juan José Carol Paz, Jorge Nicolás Gómez and Ana Estela Ledesma

Curr. Issues Mol. Biol. 2026, 48(5), 497; https://doi.org/10.3390/cimb48050497 (registering DOI) - 11 May 2026

Abstract

The rapid characterization of lactic acid bacteria (LAB) with probiotic and technological properties is crucial for functional food design. In this study, fourteen LAB strains belonging to the species Lactiplantibacillus (L.) plantarum, Lentilactobacillus (L.) parabuchneri, and Leuconostoc [...] Read more.

The rapid characterization of lactic acid bacteria (LAB) with probiotic and technological properties is crucial for functional food design. In this study, fourteen LAB strains belonging to the species Lactiplantibacillus (L.) plantarum, Lentilactobacillus (L.) parabuchneri, and Leuconostoc (L.) mesenteroides were differentiated using Raman spectroscopy. By integrating Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA), we achieved a clear inter-generic separation while simultaneously enabling the intra-specific grouping of L. plantarum strains. Our results demonstrate that the Raman spectral fingerprint, coupled with supervised chemometric models, successfully categorized the strains into three distinct clusters based on their macromolecular profiles. Specifically, the analysis provided high-resolution differentiation between genera and, more importantly, allowed for the fine-scale clustering of diverse L. plantarum isolates. This highlights Raman spectroscopy as a robust, non-destructive tool for the rapid identification and taxonomic classification of LAB, offering a high-throughput alternative to traditional molecular methods for strain-level discrimination. Full article

(This article belongs to the Special Issue Molecular Dynamics Simulations in Structural Biology: From Proteins to Complex Biomolecular Systems)

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17 pages, 1985 KB

Open AccessArticle

Potential Prognostic and Metastatic Implications of MACC1 and MMP8 in Colorectal Cancer

by Hilal Oğuz Soydinç, Sena Şen, Murat Serilmez and Senem Karabulut

Curr. Issues Mol. Biol. 2026, 48(5), 496; https://doi.org/10.3390/cimb48050496 (registering DOI) - 11 May 2026

Abstract

Colorectal cancer (CRC) remains a major cause of cancer-related morbidity and mortality worldwide. Metastasis regulators and matrix metalloproteinases have been implicated in tumor progression; however, their clinical significance in CRC remains incompletely defined. In this study, the prognostic value of MACC1 and MMP8 [...] Read more.

Colorectal cancer (CRC) remains a major cause of cancer-related morbidity and mortality worldwide. Metastasis regulators and matrix metalloproteinases have been implicated in tumor progression; however, their clinical significance in CRC remains incompletely defined. In this study, the prognostic value of MACC1 and MMP8 expression levels was investigated. A total of 140 patients diagnosed with CRC and 48 healthy controls were included. Serum levels of MACC1 and MMP8 were measured using ELISA. Clinicopathological parameters were recorded, and their associations with biomarker expression were analyzed. Both MACC1 and MMP8 levels demonstrated moderate diagnostic performance with comparable area under the curve values. A strong positive correlation between MACC1 and MMP8 expression was observed. MACC1 expression was significantly associated with metastasis status and tumor stage, whereas MMP8 expression was associated with tumor localization. In survival analyses, established clinicopathological factors, particularly tumor stage and metastasis status, were identified as the primary determinants of overall survival. In multivariate analysis, tumor stage remained the only consistent independent prognostic factor, while MMP8 showed a modest independent association in a separate model. MACC1 did not retain independent prognostic significance. Although MACC1 and MMP8 may have diagnostic and biological relevance in CRC, their prognostic utility appears limited compared to established clinical parameters. Further large-scale prospective studies are needed. Full article

(This article belongs to the Section Molecular Medicine)

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18 pages, 1746 KB

Open AccessArticle

In Vitro Anti-Inflammatory Activity and Molecular Docking Analysis of Compounds Isolated from Beyeria viscosa

by Hamza Shahid, James P. Flood, Feng Li, Xian Zhou, Gerald Münch and Ritesh Raju

Curr. Issues Mol. Biol. 2026, 48(5), 495; https://doi.org/10.3390/cimb48050495 (registering DOI) - 10 May 2026

Abstract

Inflammation contributes to the progression of numerous chronic diseases, and plants are a rich source of bioactive secondary metabolites. In this study, bioassay-guided isolation of the previously unexplored Australian native plant Beyeria viscosa (Labill.) Miq. yielded eleven known compounds (1–11 [...] Read more.

Inflammation contributes to the progression of numerous chronic diseases, and plants are a rich source of bioactive secondary metabolites. In this study, bioassay-guided isolation of the previously unexplored Australian native plant Beyeria viscosa (Labill.) Miq. yielded eleven known compounds (1–11). The chemical structures of these compounds were identified by detailed spectroscopic data analysis, and definitive structural confirmation was established using single-crystal X-ray crystallography for fritillebic acid (8) and herbacetin 3,7,8-trimethyl ether (5) for the first time. All compounds were first screened for nitric oxide (NO) inhibitory activity and cytotoxicity in lipopolysaccharide (LPS) and interferon (IFN)-γ-stimulated RAW 264.7 macrophages, and the active NO inhibitors were further assessed for tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) inhibition. Notably, compounds 5, 8, and 10 were evaluated for NO inhibitory activity for the first time, with compound 8 being the most potent (IC₅₀ = 8.8 ± 1.3 μM), compound 10 showing moderate potency (IC₅₀ = 12.2 ± 8.8 μM), and compound 5 being inactive. Among all tested compounds, fritillebic acid (8) emerged as the most active constituent, showing strong NO inhibition and moderate suppression of TNF-α and IL-6 production; therefore, it was further assessed in LPS-stimulated N-11 microglial cells, where it retained NO inhibitory activity (IC₅₀ = 12.3 ± 0.5 μM) with a favorable activity–cytotoxicity profile (LC₅₀ = 107.9 ± 1.9 μM). Consistent with the promising activity, molecular docking of compound 8 showed strong receptor-binding affinity with selected inflammation-related targets. Moreover, preliminary structure–activity relationship analysis of all isolated compounds suggested that substitution and oxygenation patterns may influence NO inhibitory potency. Overall, these findings identify fritillebic acid as the major anti-inflammatory lead from B. viscosa and highlight Australian native plants as a source of bioactive secondary metabolites. Full article

(This article belongs to the Special Issue Biologically Active Compounds: Sources, Mechanisms of Action, and Applications)

24 pages, 4840 KB

Open AccessArticle

Immune-Enhancing Effects of Polygonatum cyrtonema Polysaccharides in Immunodeficient Zebrafish

by Daoyuan Li, Jie Wang, Naifu Chen and Naidong Chen

Curr. Issues Mol. Biol. 2026, 48(5), 494; https://doi.org/10.3390/cimb48050494 (registering DOI) - 9 May 2026

Abstract

To evaluate the immune-enhancing effects of Polygonatum cyrtonema polysaccharides in vivo, an immunodeficiency zebrafish model was established by microinjecting vinorelbine tartrate into the caudal vein. Effects of the polysaccharides (500, 1000 and 2000 μg/mL) on neutrophil counts were assessed in Tg (mpx:GFP) zebrafish. [...] Read more.

To evaluate the immune-enhancing effects of Polygonatum cyrtonema polysaccharides in vivo, an immunodeficiency zebrafish model was established by microinjecting vinorelbine tartrate into the caudal vein. Effects of the polysaccharides (500, 1000 and 2000 μg/mL) on neutrophil counts were assessed in Tg (mpx:GFP) zebrafish. Transcriptome sequencing was employed to investigate the immunomodulatory effects of the polysaccharides. The results revealed a dose-dependent increase in neutrophil counts following treatment with the polysaccharides. Transcriptomic profiling identified 1286 DEGs across the three comparison groups. GO and KEGG enrichment analyses indicated that the polysaccharides could modulate immune-related pathways in the zebrafish model. Two enriched KEGG pathways, including the MAPK signaling and the mTOR signaling pathway, were utilized to analyze immune-related gene expression. To validate RNA-seq data, qRT-PCR was performed on selected DEGs, including il1b, crk, fgf10b, atp6v1aa, and eif4e1c. The results confirmed that the expression patterns of these genes were consistent with the RNA-seq data. Within the tested concentrations (500, 1000 and 2000 μg/mL), the polysaccharides exhibited a dose-dependent immunostimulatory effect, with the highest immunostimulatory response observed at 2000 μg/mL. The molecular level primarily involves the enhancement of neutrophil function through the modulation of multiple immune-related pathways. These findings provide a theoretical basis for the potential application of Polygonatum cyrtonema polysaccharides as a natural immunomodulatory agent. Full article

(This article belongs to the Section Bioorganic Chemistry and Medicinal Chemistry)

23 pages, 1618 KB

Open AccessReview

Microbial Dysbiosis in Photodermatoses: Formation, Pathogenesis and Intervention Strategies

by Lanhai Zhong, Tian Wang, Lu Tang, Jiande Han, Qun Zhao and Naiyu Lin

Curr. Issues Mol. Biol. 2026, 48(5), 493; https://doi.org/10.3390/cimb48050493 (registering DOI) - 9 May 2026

Abstract

Recent studies have reported skin microbiome dysbiosis in patients with photodermatoses, featuring enriched Staphylococcus aureus colonization and decreased microbiome diversity. We propose that ultraviolet radiation (UVR), along with atypical antimicrobial peptides, may exert selective pressure on the skin microbiome, while cytokine dysregulation and [...] Read more.

Recent studies have reported skin microbiome dysbiosis in patients with photodermatoses, featuring enriched Staphylococcus aureus colonization and decreased microbiome diversity. We propose that ultraviolet radiation (UVR), along with atypical antimicrobial peptides, may exert selective pressure on the skin microbiome, while cytokine dysregulation and a reduction in commensal bacteria amplify microbial dysbiosis. Dysbiotic microorganisms further release pathogen-associated patterns and virulence factors, and activate tissue-resident memory T cells, which collectively contribute to local inflammation. These mechanisms establish the skin microbiome as a potential target for early intervention. Potential therapeutic strategies may include antibiotics, phototherapy, bleach baths, phage therapy, and microbiota-based therapies. This review integrates current findings from microbial ecology, molecular biology, and host immunology to outline a conceptual framework linking UVR exposure, microbiome alterations, and cutaneous immune responses, while emphasizing the current limitations and evidence gaps in this field. Full article

(This article belongs to the Special Issue Exploring Molecular Pathways in Skin Health and Diseases)

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22 pages, 9093 KB

Open AccessArticle

Molecular Target Discovery and Systemic Mechanism Analysis of Teriflunomide for Dry Eye Disease

by Yang Chen, Weiran Lin, Wei Feng, Wenyuan Li and Lianhao Song

Curr. Issues Mol. Biol. 2026, 48(5), 492; https://doi.org/10.3390/cimb48050492 (registering DOI) - 9 May 2026

Abstract

Background: Dry eye disease (DED) is a multifactorial ocular surface disorder characterized by tear film instability, inflammation, and neurosensory abnormalities. Current therapies remain limited by slow onset and suboptimal efficacy. Teriflunomide, an immunomodulatory agent approved for multiple sclerosis, has shown therapeutic potential in [...] Read more.

Background: Dry eye disease (DED) is a multifactorial ocular surface disorder characterized by tear film instability, inflammation, and neurosensory abnormalities. Current therapies remain limited by slow onset and suboptimal efficacy. Teriflunomide, an immunomodulatory agent approved for multiple sclerosis, has shown therapeutic potential in DED, but its multi-target mechanisms remain unclear. Methods: We employed an integrated computational and transcriptomic framework combining ADMET profiling, multi-dataset transcriptomic integration, and single-cell RNA sequencing (scRNA-seq) to identify disease-relevant targets. Candidate genes were further refined through molecular docking and 50 ns molecular dynamics (MD) simulations. The AetherCell virtual cell model was applied to evaluate both the concordance between target perturbation and drug-induced responses and the potential mechanistic roles of candidate targets. Results: Transcriptomic integration identified 16 consensus genes across heterogeneous DED models, which were further localized to disease-relevant epithelial and immune cell populations by scRNA-seq. Molecular simulations prioritized three core targets—CTSS, STAT1, and PTGS1—based on binding stability and affinity. AetherCell simulations demonstrated that perturbation of these targets not only recapitulated teriflunomide-induced transcriptional and pathway changes but also revealed their distinct mechanistic contributions, including epithelial barrier regulation (CTSS), microvascular and lipid homeostasis (PTGS1), and inflammation suppression coupled with tissue repair (STAT1). Conclusions: Teriflunomide exerts therapeutic effects in DED through coordinated multi-target regulation involving inflammation control, barrier restoration, and tissue repair. This study provides a rationale for novel therapeutic targets in dry eye disease, establishes a paradigm for applying virtual cell modeling to elucidate drug mechanisms, and offers a bioinformatics framework for validating drug repositioning outcomes. Full article

(This article belongs to the Section Molecular Medicine)

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11 pages, 1943 KB

Open AccessArticle

Transcriptomic Profiling Identifies Potential Prognostic Genes in Vietnamese Patients with Non-Small-Cell Lung Cancer

by Tuan Quoc Bach, Giang Thi Chau Truong, Bang Ngoc Dao, Thang Ba Ta and Thuy Thi Bich Vo

Curr. Issues Mol. Biol. 2026, 48(5), 491; https://doi.org/10.3390/cimb48050491 (registering DOI) - 9 May 2026

Abstract

Background/Objectives: Non-small-cell lung cancer (NSCLC) is one of the most common malignancies in Vietnam, yet its molecular mechanisms remain incompletely understood. This study aimed to identify prognostic genes in Vietnamese NSCLC patients using integrative transcriptomic and bioinformatics analyses. Methods: RNA-seq data from 30 [...] Read more.

Background/Objectives: Non-small-cell lung cancer (NSCLC) is one of the most common malignancies in Vietnam, yet its molecular mechanisms remain incompletely understood. This study aimed to identify prognostic genes in Vietnamese NSCLC patients using integrative transcriptomic and bioinformatics analyses. Methods: RNA-seq data from 30 Vietnamese NSCLC patients treated at Military Hospital 103 (January 2023–April 2024) were analyzed and cross-validated with the Gene Expression Omnibus (GEO) dataset GSE140343 to identify shared differentially expressed genes (DEGs). Subsequent analyses included functional enrichment (GO and KEGG), protein–protein interaction (PPI) network construction via STRING, and module/centrality analyses to pinpoint hub genes. Finally, prognostic significance was evaluated using overall survival data from The Cancer Genome Atlas (TCGA) via the GEPIA platform. Results: A total of 1900 shared DEGs were identified, most of which were enriched in cancer-related pathways. The resulting PPI network (comprising 1528 nodes and 8185 edges) yielded eight significant modules containing 64 high-centrality candidate genes. Survival analyses demonstrated that high expression of CCNA2 and S100A12, and low expression of ADRB2, ARRB1, PTGS2, and SMAD7 were significantly associated with poor overall survival in NSCLC patients. Conclusions: These findings highlight potential biomarkers for prognosis and may inform future therapeutic strategies in Vietnamese NSCLC patients. Full article

(This article belongs to the Special Issue Bioinformatics in Human Disease Network Analysis)

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16 pages, 4301 KB

Open AccessArticle

Cytotoxic and Antimelanoma Activity of Selected 3-Methyl-1,6-diazaphenothiazines in Human Melanoma Cells—In Vitro Studies

by Beata Morak-Młodawska, Małgorzata Jeleń, Zuzanna Rzepka, Milena Koch and Dorota Wrześniok

Curr. Issues Mol. Biol. 2026, 48(5), 490; https://doi.org/10.3390/cimb48050490 (registering DOI) - 9 May 2026

Abstract

The cytotoxic and mechanistic effects of novel 10-substituted 3-methyl-1,6-diazaphenothiazines were investigated in human melanoma models. Antiproliferative activity was evaluated in vitro using the WST-1 assay in four melanoma cell lines (A375, C32, G361, and SK-MEL-28) and normal human dermal fibroblasts (HDF). Among the [...] Read more.

The cytotoxic and mechanistic effects of novel 10-substituted 3-methyl-1,6-diazaphenothiazines were investigated in human melanoma models. Antiproliferative activity was evaluated in vitro using the WST-1 assay in four melanoma cell lines (A375, C32, G361, and SK-MEL-28) and normal human dermal fibroblasts (HDF). Among the tested derivatives, compound 6 exhibited the most pronounced biological activity, showing the strongest growth inhibition in melanoma cells, with the lowest IC₅₀ value against C32 cells (54 µM), while displaying lower toxicity toward normal fibroblasts. Mechanistic studies using image cytometry and immunofluorescence revealed that compound 6 profoundly disrupts melanoma cell homeostasis by suppressing cell proliferation, inducing DNA damage, and activating apoptotic cell death. These effects were accompanied by mitochondrial membrane depolarization, depletion of intracellular reduced thiols, and DNA fragmentation, indicating the involvement of oxidative stress and mitochondrial dysfunction in the observed cytotoxic response. Taken together, these results demonstrate that 10-substituted 1,6-diazaphenothiazines exert anti-melanoma activity through multiple biological mechanisms. We believe our study provides a basis for developing derivatives with optimized pharmacological properties. Full article

(This article belongs to the Section Bioorganic Chemistry and Medicinal Chemistry)

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35 pages, 1245 KB

Open AccessReview

Natural Products Targeting Acetylation in Bladder Cancer: Mechanistic Basis, Therapeutic Potential, and Future Perspectives

by Wei Li, Da Liu, Qinzhamusu Yin, Yiwen Geng, Yang Liu and Yong Wang

Curr. Issues Mol. Biol. 2026, 48(5), 489; https://doi.org/10.3390/cimb48050489 - 8 May 2026

Abstract

Bladder cancer remains a major clinical challenge because of its high recurrence rate, marked molecular heterogeneity, frequent progression, and limited durability of current therapeutic strategies. Increasing evidence indicates that acetylation, as a reversible and druggable epigenetic modification, plays a central role in bladder [...] Read more.

Bladder cancer remains a major clinical challenge because of its high recurrence rate, marked molecular heterogeneity, frequent progression, and limited durability of current therapeutic strategies. Increasing evidence indicates that acetylation, as a reversible and druggable epigenetic modification, plays a central role in bladder cancer biology by linking chromatin remodeling to transcriptional regulation, DNA damage repair, metabolic adaptation, and immune modulation. Both histone and non-histone acetylation are frequently dysregulated in bladder cancer, and these alterations contribute to multiple malignant phenotypes, including sustained proliferation, defective cell-cycle control, apoptosis evasion, epithelial–mesenchymal transition, metastatic progression, and therapeutic resistance. In this review, we summarize the mechanistic basis of acetylation imbalance in bladder cancer, with particular emphasis on the roles of histone acetyltransferases, histone deacetylases, sirtuins, and acetylation-associated metabolic regulators. We further discuss the emerging evidence that natural products can modulate acetylation-related pathways in bladder cancer, mainly through targeting HDAC-dependent histone deacetylation and SIRT1-associated non-histone deacetylation. Representative compounds, including sulforaphane, erucin, puerarin, capsaicin, curcumin, trichostatin A, trichostatin C, and pinocembrin, highlight the potential of natural products to suppress tumor growth, promote apoptosis, impair migration, and enhance antitumor immunity through acetylation-related mechanisms. Beyond summarizing individual agents, the evidence was evaluated based on the integration of acetylation-related target engagement, acetylation remodeling, and bladder cancer-relevant phenotypic outcomes. The current evidence is heterogeneous. SFN/ECN, capsaicin, and pinocembrin offer the most convincing bladder cancer-specific support, whereas several other compounds remain limited by context-dependent effects, indirect pathway inference, or incomplete validation of the proposed acetylation mechanisms. These findings support an evidence-oriented translational framework that prioritizes natural products according to mechanistic robustness, bladder cancer specificity, and combination potential. Overall, acetylation-targeting natural products represent a promising but still evolving therapeutic strategy for bladder cancer, warranting further subtype-specific, mechanistically rigorous, and translationally oriented investigation. Full article

(This article belongs to the Special Issue Natural Compounds: An Adjuvant Strategy in Cancer Management, 2nd Edition)

27 pages, 2406 KB

Open AccessReview

The Potential and Prospects of Hydrogel Applications in Traumatic Brain Injury Treatment

by Cheng Zhong, Jie Li, Dengzhuo Liu, Xinran He, Zihao Fan, Xinxin Guo and Guangwei Wang

Curr. Issues Mol. Biol. 2026, 48(5), 488; https://doi.org/10.3390/cimb48050488 - 8 May 2026

Abstract

Traumatic brain injury (TBI) is a prevalent neurological disorder that induces severe neurological dysfunction and markedly reduces quality of life owing to its complex pathophysiology and limited therapeutic options. Conventional pharmacological and surgical interventions show restricted efficacy because of poor blood–brain barrier penetration [...] Read more.

Traumatic brain injury (TBI) is a prevalent neurological disorder that induces severe neurological dysfunction and markedly reduces quality of life owing to its complex pathophysiology and limited therapeutic options. Conventional pharmacological and surgical interventions show restricted efficacy because of poor blood–brain barrier penetration and inability to address secondary injury cascades. In recent years, hydrogels have shown significant potential for TBI repair due to their superior biocompatibility, high water content, and ability to mimic the native extracellular matrix (ECM). This review systematically examines recent advances in hydrogel applications for TBI therapy, focusing on their roles as drug delivery platforms, stem cell scaffolds, neuroregeneration promoters, inflammation modulators, and angiogenesis facilitators. Particular emphasis is placed on the therapeutic benefits and underlying mechanisms of ECM-derived hydrogels, self-assembling peptide (SAP) hydrogels, stimuli-responsive smart hydrogels, and functionalized multicomponent systems. Current challenges and limitations in hydrogel applications are also discussed, along with future research directions, to provide scientific rationale and practical guidance for precision TBI therapy. Full article

(This article belongs to the Special Issue The Contribution and Application of Molecular Biology in the Applied Biosciences—Focusing on Medicine, Biomaterials and Tissue Engineering Fields, 3rd Edition)

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16 pages, 2345 KB

Open AccessArticle

Coix Seed Oil Ameliorates Rheumatoid Arthritis by Modulating Inflammation-Associated Metabolic Pathways

by Yong Yang, Ying Feng, Weijie Tang, Yu Meng and Xiuping Ma

Curr. Issues Mol. Biol. 2026, 48(5), 487; https://doi.org/10.3390/cimb48050487 - 8 May 2026

Abstract

Rheumatoid arthritis (RA) is a chronic disease that primarily manifests as symmetrical joint inflammation. Although Coix Seed Oil (CSO) has demonstrated anti-inflammatory effects in RA rat models, its systemic metabolic regulatory mechanisms remain unclear. Therefore, we aimed to investigate whether CSO ameliorates RA [...] Read more.

Rheumatoid arthritis (RA) is a chronic disease that primarily manifests as symmetrical joint inflammation. Although Coix Seed Oil (CSO) has demonstrated anti-inflammatory effects in RA rat models, its systemic metabolic regulatory mechanisms remain unclear. Therefore, we aimed to investigate whether CSO ameliorates RA by modulating inflammation-associated metabolic pathways. Ultra-High-Performance Liquid Chromatography (UHPLC)-Q Exactive HF-X-MS-based metabolomics was used to profile metabolites in the synovial tissue and serum of complete Freund’s adjuvant (CFA)-induced RA rats. Systematically altered metabolites and their associated pathways were identified using multivariate analysis and pattern recognition. CSO treatment modulated 16 RA-related biomarkers in rat synovial tissues and 12 in the serum, which mainly affected amino acids, arachidonic acids, lipids, sphingolipids, and carnitines. These metabolites were associated with eight perturbed metabolic pathways that were predominantly involved in inflammatory responses. This study demonstrated that CSO has significant anti-RA effects on pharmacodynamic activity and metabolic network regulation. Additionally, inflammation-associated metabolic pathways are closely linked to the therapeutic efficacy of CSO in RA treatment. Full article

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

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20 pages, 3735 KB

Open AccessArticle

NEK1 Promotes Ovarian Cancer Progression via p53 Suppression While Enhancing Sensitivity to Genotoxic Therapy

by Huiyang Song, Xia Wang, Aiqing Yang, Xuejiao Ren, Xiaoqi Zhou, Yifei Qiu, Yating Cai, Chengming Gao, Gangqiao Zhou and Pengbo Cao

Curr. Issues Mol. Biol. 2026, 48(5), 486; https://doi.org/10.3390/cimb48050486 - 7 May 2026

Abstract

Ovarian cancer (OV) is a highly metastatic and recurrent malignancy with limited therapeutic options. NIMA-related kinase 1 (NEK1), a serine/threonine kinase implicated in cell cycle regulation and DNA damage response, has been associated with tumorigenesis in various cancers, yet its specific role in [...] Read more.

Ovarian cancer (OV) is a highly metastatic and recurrent malignancy with limited therapeutic options. NIMA-related kinase 1 (NEK1), a serine/threonine kinase implicated in cell cycle regulation and DNA damage response, has been associated with tumorigenesis in various cancers, yet its specific role in OV pathogenesis remains elusive. This study systematically investigates the oncogenic function and underlying mechanisms of NEK1 in ovarian cancer. Our findings demonstrate that NEK1 promotes tumor progression both in vitro and in vivo. Mechanistically, bioinformatic and biochemical analyses reveal that NEK1 suppresses p53 signaling activity, resulting in downregulation of downstream targets p21 and PUMA, consequently attenuating cell cycle arrest and apoptosis. Importantly, NEK1-driven oncogenicity is dependent on the presence of p53 protein. Clinically, elevated NEK1 expression significantly correlates with poorer prognosis across multiple independent OV cohorts. Paradoxically, high NEK1 expression enhances radiosensitivity by impairing p53-mediated DNA damage repair. Collectively, these findings establish NEK1 as a promising prognostic biomarker and therapeutic target, with potential utility in guiding genotoxic therapy strategies for ovarian cancer patients. Full article

(This article belongs to the Section Molecular Medicine)

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16 pages, 8515 KB

Open AccessArticle

MEOX1 Inhibits Growth and Metastasis of Salivary Adenoid Cystic Carcinoma

by Huaxiu Sun, Yuping Liu, Yajuan Cui, Zheng Zhou, Zhanlan Wu and Chuan-Xiang Zhou

Curr. Issues Mol. Biol. 2026, 48(5), 485; https://doi.org/10.3390/cimb48050485 - 6 May 2026

Abstract

Salivary adenoid cystic carcinoma (SACC) is a malignant salivary gland neoplasm characterized by aggressive local invasion and a marked propensity for metastasis. However, the role of MEOX1 in SACC progression remains poorly defined. In this study, we examined the effects of MEOX1 overexpression [...] Read more.

Salivary adenoid cystic carcinoma (SACC) is a malignant salivary gland neoplasm characterized by aggressive local invasion and a marked propensity for metastasis. However, the role of MEOX1 in SACC progression remains poorly defined. In this study, we examined the effects of MEOX1 overexpression on the malignant behavior of SACC cells in vitro and in vivo. Human SACC-83 and SACC-LM cells were transduced with lentiviral vectors encoding MEOX1 or an empty vector control, and cell proliferation, migration, invasion, and cell cycle distribution were assessed using CCK-8, wound healing, Transwell, and flow cytometric assays, respectively. RNA sequencing was performed to characterize transcriptional changes associated with MEOX1 overexpression. In vivo, tumor growth was evaluated in BALB/c nude mice bearing subcutaneous xenografts, and pulmonary metastatic colonization was assessed using a tail vein injection model. MEOX1 overexpression reduced the proliferation, migration, and invasion of SACC cells in vitro and increased the G2/M phase fraction. In xenograft models, MEOX1-overexpressing cells formed smaller tumors and showed lower Ki67 staining than control cells. In the experimental lung metastasis model, mice injected with MEOX1-overexpressing cells developed fewer pulmonary metastatic nodules. RNA-seq identified 588 differentially expressed genes associated with MEOX1 overexpression, with enrichment in pathways including cytokine–cytokine receptor interaction, Toll-like receptor signaling, and G protein-coupled receptor signaling. Together, these findings indicate that enforced MEOX1 expression is associated with reduced malignant phenotypes in SACC models and with transcriptomic alterations in pathways related to immune response, G protein-coupled receptor signaling, and DNA damage response. Full article

(This article belongs to the Special Issue Molecular Biology and Functional Roles of Tumor Suppressor Genes in Cancer)

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21 pages, 15127 KB

Open AccessArticle

The Mechanisms of Changes in Storage Substances and Hormone Levels During Artificial Aging of Different Varieties of Perilla

by Yang Hang, Jinwei Pan, Xiang Yi, Jianqin Zhang, Feng Bin, Huilin Li, Weihong Lin, Tingting Yuan and Erru Yu

Curr. Issues Mol. Biol. 2026, 48(5), 484; https://doi.org/10.3390/cimb48050484 (registering DOI) - 6 May 2026

Abstract

Seed aging is a key issue that affects the preservation of germplasm resources and crop production. At present, the anti-aging properties of perilla seeds and the mechanisms of differences among varieties have not been clearly reported. This study aims to analyze the mechanisms [...] Read more.

Seed aging is a key issue that affects the preservation of germplasm resources and crop production. At present, the anti-aging properties of perilla seeds and the mechanisms of differences among varieties have not been clearly reported. This study aims to analyze the mechanisms of changes in storage substances and hormone levels in different varieties of perilla during the artificial aging process. The results show that seed aging can significantly reduce the activity of antioxidant enzymes in perilla seeds, decrease the contents of storage nutrients such as soluble proteins, soluble sugars, and oil content, reduce the accumulation of unsaturated fatty acids such as oleic acid, linoleic acid, and linolenic acid, and significantly decrease the contents of endogenous Gibberellic acid (GA₃) and Indole-3-acetic acid (IAA). Meanwhile, the levels of hydrogen peroxide (H₂O₂) and Malondialdehyde (MDA) increased significantly, while the contents of saturated fatty acids such as palmitic acid and stearic acid rose, and the contents of endogenous Abscisic acid (ABA), Jasmonic acid (JA), Salicylic acid (SA), and Trans-zeatin riboside (TZR) were significantly upregulated. There are significant genotype differences in the tolerance of different perilla varieties to seed aging. The sensitivity of Shiban Perill (S23014) to aging stress is significantly higher than that of Qisu No. 2 (S23017). This study has confirmed that seed aging has adverse effects on the germination of perilla seeds by down-regulating the activity of antioxidant enzymes, reducing the accumulation of storage nutrients, and disrupting the balance of endogenous hormones. The research results provide an important theoretical basis for the preservation of perilla seed germplasm resources and the selection of anti-aging varieties. Full article

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

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39 pages, 3498 KB

Open AccessReview

Natural Products in Epilepsy Treatment: From Traditional Medicine Towards Computational Drug Discovery

by Muhammad Yasir, Jin-Hee Han, Jongseon Choe and Wanjoo Chun

Curr. Issues Mol. Biol. 2026, 48(5), 483; https://doi.org/10.3390/cimb48050483 - 6 May 2026

Abstract

Epilepsy affects approximately 50 million people worldwide, with nearly one-third of patients experiencing drug-resistant seizures despite available antiepileptic drugs (AEDs). Natural products remain an important source of bioactive scaffolds for drug discovery, offering diverse chemical structures capable of modulating key pathological pathways in [...] Read more.

Epilepsy affects approximately 50 million people worldwide, with nearly one-third of patients experiencing drug-resistant seizures despite available antiepileptic drugs (AEDs). Natural products remain an important source of bioactive scaffolds for drug discovery, offering diverse chemical structures capable of modulating key pathological pathways in epilepsy. This review examines major classes of natural compounds, including alkaloids, flavonoids, terpenoids, and phenolic compounds, and their activity against validated targets such as GABAergic and glutamatergic systems, voltage-gated ion channels, and neuroinflammatory pathways. Advances in computational drug discovery have significantly accelerated the identification and optimization of these compounds. Approaches such as virtual screening, molecular docking, molecular dynamics simulations, and machine learning models, particularly graph neural networks (GNNs), enable the efficient prediction of compound target interactions, binding stability, and pharmacokinetic properties, including blood–brain barrier (BBB) penetration and ADMET profiles. These methods support the prioritization and rational modification of natural product leads from large chemical libraries. Notable clinical approval of cannabidiol (Epidiolex) highlights the translational potential of natural product-based therapeutics. However, challenges such as limited bioavailability, pharmacokinetic constraints, and variability in natural sources continue to hinder development. This review provides an integrated perspective on natural product scaffolds, their molecular targets, and the computational strategies driving their advancement toward novel antiepileptic therapies. Full article

(This article belongs to the Special Issue Natural Products in Biomedicine and Pharmacotherapy, 2nd Edition)

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19 pages, 1490 KB

Open AccessArticle

Impact of a Single Hemodialysis Session on Oxidative Stress-Inducing and Oxidative Damage Biomarkers in End-Stage Kidney Disease Patients

by Athina Varemmenou, Effimia Michail, Electra Kalaitzopoulou, Polyxeni Papadea, Marianna Skipitari, Marios Papasotiriou, Evangelos Papachristou, Dimitrios Goumenos and Christos D. Georgiou

Curr. Issues Mol. Biol. 2026, 48(5), 482; https://doi.org/10.3390/cimb48050482 - 6 May 2026

Abstract

Oxidative stress (OS) is elevated in patients with end-stage kidney disease undergoing maintenance dialysis and contributes to increased cardiovascular risk. While kidney dysfunction and dialysis can generate OS, the acute effects of a single dialysis session remain unclear due to variability in study [...] Read more.

Oxidative stress (OS) is elevated in patients with end-stage kidney disease undergoing maintenance dialysis and contributes to increased cardiovascular risk. While kidney dysfunction and dialysis can generate OS, the acute effects of a single dialysis session remain unclear due to variability in study design and the biomarkers used. In this observational study, blood samples from 68 hemodialysis patients were collected before and after a single session. Plasma levels of the reactive oxygen species marker superoxide (O₂^•−) and OS-damage marker lipid hydroperoxides (LOOHs), protein-bound malondialdehyde (PrMDA), protein-bound thiobarbituric acid reactive substances (PrTBARSs), and protein carbonyls (PrCOs) were measured. LOOHs increased significantly by 50% post-dialysis, whereas PrMDA and PrTBARSs decreased modestly by ~10%. No significant changes were observed in O₂^•− or PrCOs. Dialysis vintage correlated positively with LOOHs, PrMDA, and PrTBARSs, but not with O₂^•− or PrCOs. No significant associations were found between OS markers and comorbidities, medication or sex. The post-dialysis rise in LOOHs, an early-formed and least accumulating lipid peroxidation marker, may reflect acute changes in OS during a single HD session. The rising association of PrMDA and PrTBARSs with dialysis vintage may suggest cumulative OS over time. Full article

(This article belongs to the Special Issue Molecular Research on Free Radicals and Oxidative Stress—2nd Edition)

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19 pages, 2359 KB

Open AccessArticle

Exploring Hydroxytyrosol as a Promising Virucidal Agent: In Silico and In Vitro Insights into Enveloped Viruses

by Hanan El Ouadi, Zineb Rhazzar, Barbara Poddesu, Boutaina Addoum, Laila Benbacer, Franco Lori, Siham Fellahi, Davide De Forni, Omar Nyabi, Jean-Luc Gala, Elmostafa El Fahime, Saber Boutayeb, Lahcen Belyamani, Khalid Ennibi, Ouafae Fassi Fihri and Nadia Touil

Curr. Issues Mol. Biol. 2026, 48(5), 481; https://doi.org/10.3390/cimb48050481 - 5 May 2026

Abstract

The research investigates synthetic hydroxytyrosol (HT) antiviral properties against enveloped and non-enveloped viruses using in silico and in vitro methods. Molecular docking and ADMET analyses suggested favorable interactions of HT with ceramide and sphingomyelin (binding energies of −6.0 and −5.9 kcal/mol, respectively). Favorable [...] Read more.

The research investigates synthetic hydroxytyrosol (HT) antiviral properties against enveloped and non-enveloped viruses using in silico and in vitro methods. Molecular docking and ADMET analyses suggested favorable interactions of HT with ceramide and sphingomyelin (binding energies of −6.0 and −5.9 kcal/mol, respectively). Favorable predicted pharmacokinetics and safety profiles were also observed. In vitro tests provided preliminary evidence of the dose- and time-dependent virucidal effect of HT against several enveloped viruses, including HSV-1, West Nile virus, SARS-CoV-2 and various influenza A subtypes, which resulted in substantial viral load decreases at 1000 µg/mL. The viral titer of the measles virus decreased by 4.62 log₁₀ units during the 2 h of exposure. No virucidal activity was observed against the non-enveloped bovine rotavirus. Overall, these findings suggest that hydroxytyrosol may represent a promising candidate for further investigation as a virucidal agent, particularly against enveloped viruses. Full article

(This article belongs to the Special Issue Novel Pharmacological Strategies and Molecular Mechanisms in Nonclinical Research)

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28 pages, 11956 KB

Open AccessArticle

Comparative Whole Genome Analysis and Targeted Validation of Variants in Three Greek Indigenous Sheep Breeds

by Maria-Anna Kyrgiafini, Georgios Stamatellos, Costas Stamatis and Zissis Mamuris

Curr. Issues Mol. Biol. 2026, 48(5), 480; https://doi.org/10.3390/cimb48050480 - 5 May 2026

Abstract

Indigenous sheep breeds represent valuable reservoirs of genetic diversity shaped by long-term adaptation to local environments and management systems. Greek autochthonous sheep breeds remain underrepresented in genomic and functional studies. The objective of this study was to characterize and compare coding sequence variation [...] Read more.

Indigenous sheep breeds represent valuable reservoirs of genetic diversity shaped by long-term adaptation to local environments and management systems. Greek autochthonous sheep breeds remain underrepresented in genomic and functional studies. The objective of this study was to characterize and compare coding sequence variation in three indigenous Greek sheep breeds—Lesvos (LES), Serres (SER), and Thrace (THR)—and to identify shared and breed-associated functional patterns. The study was designed using a two-stage approach, comprising a discovery (exploratory) phase and a validation phase. In the discovery phase, whole genome sequencing data (one animal per breed; total n = 3; mean sequencing depth ~36.9×) were analyzed to identify protein-altering exonic variants, focusing on missense single-nucleotide polymorphisms (SNPs) and exonic insertions/deletions (indels). Variants were examined at breed-specific and comparative levels, followed by functional enrichment analyses using Gene Ontology (GO) and KEGG pathways. Normalized variant density metrics identified genes with elevated polymorphism levels. In the validation phase, a subset of prioritized missense SNPs was genotyped in an independent cohort of 54 animals (18 per breed) using MassARRAY genotyping. Genes harboring prioritized missense SNPs showed a conserved enrichment profile across breeds, dominated by genome maintenance, DNA repair, cytoskeletal organization, and core regulatory functions. Distinct breed-associated patterns were also observed. LES showed enrichment in metabolic, biosynthetic, and sensory-related processes, SER in regulatory and signaling functions, and THR in cytoskeletal, extracellular matrix, and organelle-associated pathways. Polymorphism density analyses highlighted highly variable genes across breeds, including olfactory receptor (OR) gene families, keratin-associated protein genes (KRTAPs), and loci involved in immune and regulatory functions (e.g., PRKDC, CDH15). The validation phase confirmed the expected allele frequency patterns for most prioritized SNPs, supporting the robustness of the approach. This study identifies functionally relevant coding variation across Greek indigenous sheep breeds, revealing conserved genomic patterns and breed-associated signatures linked to metabolic, structural, and regulatory processes. Full article

(This article belongs to the Special Issue Technological Advances Around Next-Generation Sequencing Application, 2nd Edition)

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52 pages, 2994 KB

Open AccessReview

Plant Terpenoids in Cardioprotection: An Overview of Their Therapeutic Potential

by José L. Ríos-López, José Blanco-Salas, Guadalupe Cumplido-Laso and María P. Hortigón-Vinagre

Curr. Issues Mol. Biol. 2026, 48(5), 479; https://doi.org/10.3390/cimb48050479 - 5 May 2026

Abstract

Cardiovascular diseases are the leading cause of morbidity and mortality worldwide, making the search for new therapeutic strategies to prevent or mitigate cardiac damage mandatory. Essential oils, long used in traditional medicine, contain terpenoids as their most prominent constituents, and these molecules have [...] Read more.

Cardiovascular diseases are the leading cause of morbidity and mortality worldwide, making the search for new therapeutic strategies to prevent or mitigate cardiac damage mandatory. Essential oils, long used in traditional medicine, contain terpenoids as their most prominent constituents, and these molecules have emerged as promising cardioprotective agents. The review compiles 45 articles investigating the effects of plant-derived terpenoids on cardiovascular health. Evidence shows that their therapeutic properties rely on their antioxidant, anti-inflammatory, anti-apoptotic, anti-remodeling, antiarrhythmic, antihypertensive, anti-atherosclerotic, antidiabetic and antimicrobial actions. These effects result from the modulation of molecular pathways altered during cardiovascular diseases, resulting in oxidative stress, inflammation, cell death, fibrosis, ion channel dysregulation, alteration of lipid metabolism and glucose homeostasis. Key mechanisms of terpenes healing properties include activation of endogenous antioxidant defense—mainly via Nrf2-, inhibition of NLRP3 inflammosome-mediated pyroptosis and reduction in lipid oxidation involved in atherosclerotic plaque formation. Their therapeutic potential is reinforced by low toxicity profiles and broad botanical availability. However, challenges related to their translation to therapeutic practice remain unresolved, such as low bioavailability, limited yield and scarce results in human in vitro models. Future research should focus on nano- and micro-delivery systems, biotechnological production strategies and the use of human induced pluripotent stem cell-derived cardiomyocytes. Despite these limitations, terpenes represent valuable templates for developing more potent and clinically viable therapeutic agents. Further studies of this family are encouraged due to its promising ability to treat cardiovascular disorders. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Bioactive Compounds in the Management of Human Diseases: 2nd Edition)

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