Current Issues in Molecular Biology

1 pages, 140 KB

Open AccessCorrection

Correction: Lai et al. Association Between Catenin Beta-1 (CTNNB1) Gene Polymorphisms and Non-Traumatic Osteonecrosis of the Femoral Head (ONFH). Curr. Issues Mol. Biol. 2026, 48, 164

by I-Chang Lai, De-Yi Liu, Shih-Chan Hsu and Shu-Jui Kuo

Curr. Issues Mol. Biol. 2026, 48(5), 504; https://doi.org/10.3390/cimb48050504 (registering DOI) - 14 May 2026

Abstract

In the published article [...] Full article

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

27 pages, 2295 KB

Open AccessArticle

Phytochemical Analysis, GC-MS Chemical Profiling, and In Vitro Antidiabetic Evaluation of South African Momordica balsamina Linn Leaf Extracts and Its Effects on Oxidative Stress Modulation

by Buang Matseke, Daniel Tswaledi and Kokoette Bassey

Curr. Issues Mol. Biol. 2026, 48(5), 503; https://doi.org/10.3390/cimb48050503 (registering DOI) - 13 May 2026

Abstract

Background: Momordica balsamina L. is widely used in traditional medicine for the management of diabetes in South Africa and globally. This study evaluated the in vitro antidiabetic and cytotoxic effects of M. balsamina leaf extracts and identified bioactive compounds potentially responsible for its [...] Read more.

Background: Momordica balsamina L. is widely used in traditional medicine for the management of diabetes in South Africa and globally. This study evaluated the in vitro antidiabetic and cytotoxic effects of M. balsamina leaf extracts and identified bioactive compounds potentially responsible for its activity. Methods: Leaves were sequentially extracted using solvents of increasing polarity. Phytochemical composition was determined using standard colorimetric assays, while gas chromatography–mass spectrometry (GC–MS) was employed for compound identification. Antioxidant activity was evaluated using dot blot, DPPH radical scavenging, hydrogen peroxide scavenging, and ferric reducing power assays. Antidiabetic potential was assessed using α-amylase, α-glucosidase, and β-glucosidase inhibitory assays, with acarbose as the reference drug. Cytotoxicity was determined by using the MTT assay on Vero and HEK-293 cell lines. Results: Phytochemical screening revealed alkaloids, flavonoids, terpenoids, saponins, glycosides, and steroids. GC–MS analysis identified compounds associated with antidiabetic activity, including vanillin, 2,4-di-tert-butylphenol, oleic acid, phytol, and hexadecenoic acid. All extracts exhibited antioxidant activity, with the ethyl acetate extract showing the strongest effect. Enzyme inhibition was concentration dependent. The dichloromethane and ethyl acetate extracts showed stronger α-amylase inhibition (IC₅₀ = 0.149 and 0.146 mg/mL) than acarbose (0.209 mg/mL). For α-glucosidase, acarbose showed the highest activity, while extracts displayed moderate inhibition. In β-glucosidase assays, both extracts were more active than acarbose. Both extracts were non-cytotoxic up to 500 µg/mL. Conclusions: These findings support the traditional use of M. balsamina and highlight its potential as a safe source of antidiabetic agents, warranting further investigation. Full article

(This article belongs to the Special Issue Advances in Phytochemical Research: Molecular Pathways in Health and Disease)

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20 pages, 896 KB

Open AccessReview

Molecular Subtypes of Pancreatic Cancer: A Review of the Literature

by Jakub Wnuk, Wiktoria Skowron, Anna Długaszek, Joanna Sadurska, Łukasz Pietrzyński, Jacek Kabut and Iwona Gisterek-Grocholska

Curr. Issues Mol. Biol. 2026, 48(5), 502; https://doi.org/10.3390/cimb48050502 (registering DOI) - 13 May 2026

Abstract

Pancreatic cancer (PC) is considered one of the deadliest cancers worldwide, and the number of PC-related deaths is expected to increase. Early diagnosis of PC is crucial for improving treatment outcomes. Despite improvements in overall survival (OS) in metastatic and unresectable PC due [...] Read more.

Pancreatic cancer (PC) is considered one of the deadliest cancers worldwide, and the number of PC-related deaths is expected to increase. Early diagnosis of PC is crucial for improving treatment outcomes. Despite improvements in overall survival (OS) in metastatic and unresectable PC due to systemic therapy, there is still a need to search for novel therapies and factors predictive of response to treatment. Cancer profiling based on genome sequencing can be used to develop targeted therapies and improve prognostics and treatment outcomes. Therefore, this review was conducted to evaluate the clinical value of molecular subtyping in pancreatic cancer as a prognostic and predictive factor in pancreatic cancer. Due to its limitations, including the lack of a registered protocol and risk of bias assessment for the included studies and those whose results were not included, this study should be considered a narrative review with a structured search strategy rather than a systematic review. Full article

(This article belongs to the Special Issue Molecular Approaches in Early Detection and Targeted Therapies for Pancreatic Cancer)

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18 pages, 15316 KB

Open AccessArticle

Sodium Butyrate Attenuates Isoprenaline-Induced Myocardial Injury via Restoring the Gut–Heart Axis and Suppressing TLR4/NF-κB Signaling

by Hazrat Bilal, Imran Khan, Ayesha Yaseen, Xiaopeng Zhang, Xuexue Liu, Jian Zhao, Jing Li, Ata Ur Rehman, Lei Sun and Xiao Yu

Curr. Issues Mol. Biol. 2026, 48(5), 501; https://doi.org/10.3390/cimb48050501 (registering DOI) - 13 May 2026

Abstract

The gut–heart axis plays a role in cardiac injury due to the disruption of barriers, endotoxemia, and inflammatory signaling; yet, it is not clear whether sodium butyrate (SB) is capable of alleviating isoprenaline-induced myocardial injury through coordinated intestinal, microbial, and metabolic restoration. This [...] Read more.

The gut–heart axis plays a role in cardiac injury due to the disruption of barriers, endotoxemia, and inflammatory signaling; yet, it is not clear whether sodium butyrate (SB) is capable of alleviating isoprenaline-induced myocardial injury through coordinated intestinal, microbial, and metabolic restoration. This study used male Sprague-Dawley rats, which were grouped into control, control + SB, isoprenaline (ISO)-induced myocardial injury, and ISO + SB groups. We evaluated cardiac biomarkers of injury, oxidative stress, histopathologic, intestinal barrier (16S rRNA sequencing), and serum metabolomics (LC-MS). SB treatment decreased serum cardiac troponin I, creatine kinase-MB, and lactate dehydrogenase; relieved oxidative stress; and lowered myocardial necrosis and fibrosis. It re-established colonic architecture, upregulated the expression of ZO-1 (zonula occludens-1) and claudin-1, and reduced endotoxin in the bloodstream. SB also prevented the production of proinflammatory cytokines such as TNF-α, IL-6, and IL-1β; cardiac TLR4; IκBα degradation; and NF-κB p 65 phosphorylation. In addition, SB altered the gut microbiota in favor of beneficial commensals, including Ligilactobacillus and Bifidobacterium, and reduced Desulfovibrio. It normalized key circulating metabolites and enriched cardiometabolic pathways, and the patterns of correlation suggested the coordinated remodeling of the microbiome–metabolome. These findings reveal that SB prevents myocardial injury caused by ISO through strengthening gut barrier protection, alleviating endotoxemia, inhibiting TLR4/NF-κB, and remodeling the microbiome–metabolome axis, indicating its potential for use as a gut-targeted cardioprotective intervention. Full article

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

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23 pages, 3793 KB

Open AccessArticle

DNA Barcoding and Comparative Chloroplast Marker Performance in Endemic Plants of Crete (Greece)

by Dimitra Ioannidou, Ioulietta Samartza, Georgios Tsoktouridis, Andreas D. Drouzas and Nikos Krigas

Curr. Issues Mol. Biol. 2026, 48(5), 500; https://doi.org/10.3390/cimb48050500 (registering DOI) - 13 May 2026

Abstract

Crete, a major Mediterranean biodiversity hotspot, hosts many local endemic, threatened and/or protected plant taxa (species and subspecies). Besides their ecological and conservation significance, these unique phytogenetic resources hold significant economic potential for sustainable utilization. Since DNA barcoding is critical for conservation, taxonomy, [...] Read more.

Crete, a major Mediterranean biodiversity hotspot, hosts many local endemic, threatened and/or protected plant taxa (species and subspecies). Besides their ecological and conservation significance, these unique phytogenetic resources hold significant economic potential for sustainable utilization. Since DNA barcoding is critical for conservation, taxonomy, and plant-derived product authentication, we studied 15 local Cretan endemic taxa using three chloroplast DNA (cpDNA) regions (rbcL, trnL, trnH-psbA). A comparative analysis against GenBank (NCBI) records revealed significant new data: (i) the first genetic information for five taxa (Centaurea redempta subsp. redempta, Galium fruticosum, Micromeria hispida, Salix kaptarae, Teucrium cuneifolium); (ii) new marker-specific sequences for seven taxa (Helichrysum heldreichii, Scutellaria hirta, Sesleria doerfleri, Staehelina petiolata, Teucrium alpestre, Campanula pelviformis, Phlomis lanata); and (iii) novel genotypes of already represented markers for three species (Phlomis lanata, Scutellaria sieberi, Staehelina petiolata). Phylogenetic analyses were performed for all three molecular markers across selected members of Scutellaria section Scutellaria, Teucrium section Polium, and Campanula section Quinqueloculares. The overall results indicated that, amongst the studied species, the trnH-psbA marker is more suitable for species-level identification, whereas the rbcL and trnL markers were more helpful to genus-level identification within Lamiaceae and Campanulaceae. These results enrich the DNA barcoding reference library and form a concrete contribution towards the protection, conservation and traceability of Crete’s unique botanical heritage. Full article

(This article belongs to the Special Issue Molecular Breeding and Genetics Research in Plants—3rd Edition)

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26 pages, 1714 KB

Open AccessReview

Oncolytic Herpes Simplex Virus for Glioblastoma: Molecular Engineering, Tumor Microenvironment Barriers, and Clinical Translation

by Jiayu Liu, Yuxin Wang, Zhao Gao, Tongtan Liu, Ao Xu, Wenxuan Li, Mei Li, Xiaomeng Song, Baorui Guo, Huadong Wang, Wenying Lv and Jianning Zhang

Curr. Issues Mol. Biol. 2026, 48(5), 499; https://doi.org/10.3390/cimb48050499 (registering DOI) - 13 May 2026

Abstract

Glioblastoma (GBM) remains the most aggressive primary malignant brain tumor in adults, with limited survival benefit from the current standard of care consisting of maximal safe resection, radiotherapy, and temozolomide-based chemotherapy. The highly infiltrative growth pattern, profound intratumoral heterogeneity, and strongly immunosuppressive tumor [...] Read more.

Glioblastoma (GBM) remains the most aggressive primary malignant brain tumor in adults, with limited survival benefit from the current standard of care consisting of maximal safe resection, radiotherapy, and temozolomide-based chemotherapy. The highly infiltrative growth pattern, profound intratumoral heterogeneity, and strongly immunosuppressive tumor microenvironment together contribute to therapeutic resistance and frequent recurrence. In this context, oncolytic herpes simplex virus (oHSV) has emerged as a promising therapeutic platform for glioblastoma because of its dual capacity to directly lyse tumor cells and stimulate antitumor immune responses. In addition, the large viral genome and well-characterized biology of herpes simplex virus enable extensive genetic engineering to improve tumor selectivity, safety, and immunomodulatory function. In this review, we summarize the molecular design strategies that have driven the development of oHSV for glioblastoma, including attenuation of neurovirulence, enhancement of tumor-selective replication, and arming with immune-stimulatory transgenes. We further discuss the major biological barriers within the GBM tumor microenvironment that continue to limit therapeutic efficacy, with particular attention given to representative engineered oHSV platforms and the lessons learned from preclinical and early-phase clinical studies. A dedicated section examines these barriers in detail, including restricted intratumoral viral spread, antiviral innate immunity, and immunosuppressive myeloid cell dominance. We also review current efforts to improve outcomes through rational combination strategies with radiotherapy, immune checkpoint blockade, cytokine modulation, and other multimodal approaches. Although encouraging advances have been achieved, the clinical translation of oHSV therapy for glioblastoma still faces substantial challenges in patient selection, delivery optimization, response assessment, and treatment integration. A deeper understanding of virus–host–tumor interactions and more precise engineering of viral platforms may help unlock the full potential of oHSV-based therapy. Overall, oHSV represents one of the most compelling translational approaches in glioblastoma and provides a valuable framework for the development of mechanism-driven viro-immunotherapy in neuro-oncology. Full article

(This article belongs to the Special Issue Advanced Research in Glioblastoma and Neuroblastoma)

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24 pages, 24670 KB

Open AccessReview

Revision of Energy Metabolism Adaptations in High-Level Athletes: From Physical Performance Enhancement to Potential Therapeutic Targets in Mental Disorders

by Ane Larrea, Mariyem Naji, Marina Gulak, Maria Torrecilla and Gabriel Barreda-Gómez

Curr. Issues Mol. Biol. 2026, 48(5), 498; https://doi.org/10.3390/cimb48050498 (registering DOI) - 11 May 2026

Abstract

High-level athletic performance requires the implementation of personalized strategies based on the analysis of metabolic pathways involved in energy production: phosphagen, glycolytic, and oxidative pathways. In this context, mitochondria play an essential role as the central regulator of energy production, being closely linked [...] Read more.

High-level athletic performance requires the implementation of personalized strategies based on the analysis of metabolic pathways involved in energy production: phosphagen, glycolytic, and oxidative pathways. In this context, mitochondria play an essential role as the central regulator of energy production, being closely linked to these three pathways. Exercise boosts cellular respiration, which can also be optimized by nutritional interventions and targeted supplementation, promoting mitochondrial biogenesis, reducing oxidative stress and increasing ATP production. These metabolic adaptations improve athletic performance, accelerate recovery processes, and reduce the risk of injury, adapting to the physiological characteristics of each athlete. Moreover, some of these metabolic adaptations converge on specific targets whose expression or activity is also altered in mental disorders. Therefore, the aim of this review is to analyze mitochondrial adaptations induced by exercise and supplementation, evaluating their impact on the phosphagen, glycolytic, and oxidative metabolic pathways, as well as their relationship with optimizing performance and recovery in high-level athletes, with special attention to their potential application to mental health. Full article

(This article belongs to the Special Issue Recent Advances in Energy Metabolism)

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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, 1438 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 (registering DOI) - 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)

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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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