Current Issues in Molecular Biology

17 pages, 4973 KB

Open AccessArticle

Eleutheroside E Ameliorates D-Gal-Induced Senescence in Human Skin Fibroblasts Through PI3K/AKT Signaling

by Xiangyu Ma, Liu Han, Mengran Xu, Yuling Feng, Changsheng Liu, Yida Zhao, Min Zhang, Guanghua Xu and Xin Sun

Curr. Issues Mol. Biol. 2025, 47(11), 895; https://doi.org/10.3390/cimb47110895 (registering DOI) - 28 Oct 2025

Abstract

Eleutheroside E (EE), a natural compound, shows promise in mitigating cellular senescence—a key factor in skin aging—though its mechanisms remain incompletely understood. This study integrated network pharmacology, molecular docking, and cellular experiments to explore the protective effects and mechanistic basis of EE against [...] Read more.

Eleutheroside E (EE), a natural compound, shows promise in mitigating cellular senescence—a key factor in skin aging—though its mechanisms remain incompletely understood. This study integrated network pharmacology, molecular docking, and cellular experiments to explore the protective effects and mechanistic basis of EE against D-galactose (D-gal)-induced senescence in human skin fibroblasts (HSFs). Network pharmacology analyses suggested EE’s involvement in inflammation-related pathways, especially phosphatidylinositol 3-kinase and protein kinase B (PI3K-AKT) and hypoxia-inducible factor 1 (HIF-1) signaling, which were corroborated by molecular docking revealing strong binding affinities between EE and key targets such as hypoxia-inducible factor 1-alpha (HIF1A), AKT serine/threonine kinase 1 (AKT1), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PI3Kγ), and interleukin-6 (IL-6). Cellular assays showed that EE markedly lowered oxidative stress markers, including reactive oxygen species (ROS) and malondialdehyde (MDA), reduced senescence-associated beta-galactosidase (SA-β-gal) activity, and boosted antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT). Additionally, EE dose-dependently inhibited apoptosis and downregulated PI3K/AKT phosphorylation as well as the B-cell lymphoma 2-associated X protein/B-cell lymphoma-2 (Bax/Bcl-2) ratio. These findings suggest that EE alleviates cellular senescence in HSFs mainly via the PI3K/AKT pathway by attenuating oxidative stress and apoptosis, highlighting its potential as a therapeutic agent for anti-aging strategies. Full article

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

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11 pages, 3859 KB

Open AccessArticle

Establishment of Genetic Transformation System of Non-Embryogenic Callus in Rosa rugosa

by Xinyun Liu, Xiyang Zhu, Yating Yang, Guo Wei, Liguo Feng and Mengjuan Bai

Curr. Issues Mol. Biol. 2025, 47(11), 894; https://doi.org/10.3390/cimb47110894 (registering DOI) - 28 Oct 2025

Abstract

Rosa rugosa (R. rugosa) is a commercially important ornamental species within the genus Rosa, highly valued in the horticultural market. With the increasing availability and improved annotation of Rosa genomes, establishing an efficient genetic transformation system has become essential for validating [...] Read more.

Rosa rugosa (R. rugosa) is a commercially important ornamental species within the genus Rosa, highly valued in the horticultural market. With the increasing availability and improved annotation of Rosa genomes, establishing an efficient genetic transformation system has become essential for validating candidate gene functions. As a common intermediate tissue in plant regeneration, callus has been successfully used to establish genetic transformation systems in numerous species. In this study, we characterized the morphological and physiological differences between embryogenic and non-embryogenic calli in R. rugosa. The embryogenic callus exhibited significantly higher catalase (CAT) activity and proline (PRO) content than the non-embryogenic callus. However, its growth rate was markedly slower. Antibiotic sensitivity assays identified the optimal selection concentrations for non-embryogenic callus as 35 mg/L for kanamycin and 13 mg/L for hygromycin. We subsequently introduced the phytoene synthase (RrPSY1) gene into non-embryogenic callus, with positive transformants identified using GFP fluorescence detection and PCR analysis. The overexpression of RrPSY1 significantly increased the yellow pigment substances in the callus, confirming the establishment of an effective genetic transformation system for non-embryogenic calli in R. rugosa. This system provides a useful technical platform for the manipulation of metabolic products and the verification of related gene functions in rose. Full article

(This article belongs to the Section Molecular Plant Sciences)

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19 pages, 3678 KB

Open AccessArticle

miR-7704-Enriched Stem Cell-Derived Extracellular Vesicles Attenuate Hyperoxia-Induced Apoptosis and Oxidation in Lung Epithelial Cells

by Yu-Hsun Chang, Kun-Chi Wu and Dah-Ching Ding

Curr. Issues Mol. Biol. 2025, 47(11), 893; https://doi.org/10.3390/cimb47110893 (registering DOI) - 28 Oct 2025

Abstract

Bronchopulmonary dysplasia (BPD) is a significant complication of hyperoxia in preterm neonates. Extracellular vesicle (EV)-based therapies derived from mesenchymal stem cells (MSCs) show regenerative potential. We investigated the therapeutic efficacy of EVs derived from human umbilical cord mesenchymal stem cells (HUCMSCs), particularly those [...] Read more.

Bronchopulmonary dysplasia (BPD) is a significant complication of hyperoxia in preterm neonates. Extracellular vesicle (EV)-based therapies derived from mesenchymal stem cells (MSCs) show regenerative potential. We investigated the therapeutic efficacy of EVs derived from human umbilical cord mesenchymal stem cells (HUCMSCs), particularly those engineered to overexpress miR-7704 in a hyperoxia-induced BPD cell model. EVs were isolated from GFP- and miR-7704-transfected HUCMSCs. A549 alveolar epithelial cells were exposed to normoxic or hyperoxic conditions and treated with HUCMSC-EV or miR-7704-HUCMSC-EV. EV uptake was confirmed using fluorescence microscopy. Cell proliferation was evaluated, and apoptosis was assessed by means of Western blot analysis of caspase family proteins and apoptosis-related markers. Both HUCMSC-EV and miR-7704-HUCMSC-EV enhanced A549 cell proliferation under hyperoxic stress, with miR-7704-HUCMSC-EV showing greater efficacy. Protein-level analyses revealed hyperoxia-induced increases in cleaved caspase-3, caspase-7, and FasL, along with decreased Bcl-2. Treatment with miR-7704-HUCMSC-EV significantly reversed these effects, whereas HUCMSC-EVs minimally impacted apoptotic protein expression. Bioinformatic analysis predicted that hsa-miR-7704 targeted the 3′ UTR of APOPT1. miR-7704-HUCMSC EVs also enhanced the expression of key antioxidant enzymes, including SOD1, SOD2, and HO-1. miR-7704-enriched HUCMSC-derived EV significantly promoted cell survival and mitigated hyperoxia-induced apoptosis and oxidation in a BPD cell model, suggesting their potential therapeutic role in neonatal lung injury. Full article

(This article belongs to the Section Molecular Medicine)

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13 pages, 1967 KB

Open AccessArticle

Deciphering the Anti-Cancer Efficacy of the Combination of Small-Molecule Inhibitor KAN0438757 and Curcumin in Lung Cancer Cell Lines

by Deniz Özdemir and Can Ali Ağca

Curr. Issues Mol. Biol. 2025, 47(11), 892; https://doi.org/10.3390/cimb47110892 (registering DOI) - 28 Oct 2025

Abstract

Lung cancer is among the most aggressive malignancies, with the highest incidence and mortality rates worldwide. Standard treatments include surgery, radiotherapy, and chemotherapy; however, chemoresistance often develops, reducing therapeutic efficacy. Combination therapy offers a promising strategy to enhance drug effectiveness and overcome resistance. [...] Read more.

Lung cancer is among the most aggressive malignancies, with the highest incidence and mortality rates worldwide. Standard treatments include surgery, radiotherapy, and chemotherapy; however, chemoresistance often develops, reducing therapeutic efficacy. Combination therapy offers a promising strategy to enhance drug effectiveness and overcome resistance. In lung cancer, the increased energy demands within cells result in a marked rise in the expression of PFKFB3, a regulatory protein involved in the glucose metabolic pathway. The small-molecule inhibitor KAN0438757, recognized as a novel PFKFB3 inhibitor, is significant in targeted therapy due to its essential role in the DNA damage response mechanism in cancer cells. Curcumin, the primary bioactive compound found in the rhizomes of Curcuma longa, has demonstrated a variety of biological functions and anticancer properties. This study aimed to evaluate the anticancer effects of KAN0438757 in combination with curcumin in lung cancer cells. Evaluation of cell viability and IC₅₀ values (KAN0438757: A549, 41.13 µM; H1299, 53.74 µM; Curcumin: A549, 44.37 µM; H1299, 66.25 µM) using the WST-1 and RTCA assays revealed pronounced inhibition of proliferation in the combination groups, accompanied by decreased cell migration (fold change, untreated cell; 1, CUR 20 µM; 0.681, KAN 20 µM; 0.530, and COMB; 0.0039 for 48 h). The comet assay revealed severe DNA damage (Tail DNA, fold change, untreated cell; 1, CUR 20 µM; 1.2, KAN 20 µM; 3, and COMB; 4.6) in the A549 cells, while MMP analysis (color change from red to green) and apoptotic staining confirmed cell death morphologically (color change from green to orange). Moreover, Western blot analysis demonstrated that the combination markedly enhanced apoptosis in the A549 cells. Full article

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

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16 pages, 1968 KB

Open AccessArticle

Effect of Different Prebiotic Saccharides on Listeria monocytogenes Adherence to Human Adenocarcinoma Caco-2 Cell Line

by Tereza Kodešová, Ivo Doskočil, Eva Vlková and Hana Šubrtová Salmonová

Curr. Issues Mol. Biol. 2025, 47(11), 891; https://doi.org/10.3390/cimb47110891 (registering DOI) - 28 Oct 2025

Abstract

Listeria monocytogenes (LM) is one of the most emerging pathogens responsible for the serious foodborne disease listeriosis. The risk of disease outbreaks can be reduced by suppressing the adherence of LM to the intestinal epithelial cells. This effect can be achieved by prebiotic [...] Read more.

Listeria monocytogenes (LM) is one of the most emerging pathogens responsible for the serious foodborne disease listeriosis. The risk of disease outbreaks can be reduced by suppressing the adherence of LM to the intestinal epithelial cells. This effect can be achieved by prebiotic supplementation. The aim of this work was to determine the effect of prebiotics beta-(1,3)-D-glucan, inulin, fructooligosaccharides, galactooligosaccharides, lactulose, raffinose, stachyose, human milk oligosaccharides (HMOs), and 2’-fucosyllactose on the ability of LM to adhere to the human adenocarcinoma Caco-2 cell line. Despite strain-specific variability, a statistically significant reduction in LM adhesion to intestinal epithelial cells was observed in the presence of beta-(1,3)-D-glucan (~60% reduction), inulin (~46%), and HMOs (~44%). In contrast, the remaining tested prebiotics did not show a significant impact on LM adhesion. These findings highlight the potential of specific prebiotics, especially beta-glucans, to limit LM adherence, suggesting a protective effect for the host. Full article

(This article belongs to the Special Issue Applications of Natural and Pseudo-Natural Products in Drug Discovery and Development 2025)

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19 pages, 2753 KB

Open AccessArticle

Intestinal Microbial Profiles of Wild Zobaidy (Pampus argenteus) Fish Characterized by 16S rRNA Next Generation Sequencing

by Dina Albaijan, Dalal Albaijan and Abrar Akbar

Curr. Issues Mol. Biol. 2025, 47(11), 890; https://doi.org/10.3390/cimb47110890 (registering DOI) - 28 Oct 2025

Abstract

Pampus argenteus (Zobaidy) is an important fish in Kuwait and the Gulf region due to its economic value in the fish industry. Analyzing the gut microbiome of Zobaidy can help determine the health status of the fish and its responses to environmental changes. [...] Read more.

Pampus argenteus (Zobaidy) is an important fish in Kuwait and the Gulf region due to its economic value in the fish industry. Analyzing the gut microbiome of Zobaidy can help determine the health status of the fish and its responses to environmental changes. In this study, we investigated the microbiome composition of the intestinal tract among seven wild-caught silver pomfret specimens sampled in the Arabian gulf. The 16S rRNA was sequenced using the Illumina platform; then, sequences were analyzed using several bioinformatics tools to identify the microbial diversity, taxonomical status, and functional aspects. The results were 5933 operational taxonomic units (OTUs) categorized into 35 phyla. Proteobacteria, Firmicutes, Bacteroidota, and Actinobacterota were most abundant in the Zobaidy and water samples. At the genus level, we found high relative abundances of Acinetobacter. The results indicated that Lactococcus piscium, Enterococcus cecorum, Psychrobacter arenosus, Vagococcus salmoninarum, and Carnobacterium maltaromaticum are the most commonly present species in the analyzed Zobaidy samples. A heatmap analysis indicated notable differences in the functional categories of intestinal microflora within the Zobaidy2 sample compared to other Zobaidy samples. It should be noted that microbiome studies can provide novel ways to enhance the overall welfare of fish, strengthen disease prevention, and increase sustainability in aquaculture production. Full article

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

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12 pages, 4176 KB

Open AccessArticle

Myocardium miRNA Analysis Reveals Potential Biomarkers of Sudden Coronary Death in Rats

by Chunmei Zhao, Xinyu Zhou, Yaqin Bai, Zhenxiang Zhao, Huaping Zhang, Cairong Gao, Keming Yun and Xiangjie Guo

Curr. Issues Mol. Biol. 2025, 47(11), 889; https://doi.org/10.3390/cimb47110889 (registering DOI) - 28 Oct 2025

Abstract

This study aims to provide potential biomarkers and reveal the molecular mechanism of sudden coronary death (SCD). Rat models of atherosclerotic death (ASD), coronary atherosclerosis (AS), and acute myocardial ischemia (AMI) and sham groups were established via the gavage of high-fat emulsion and [...] Read more.

This study aims to provide potential biomarkers and reveal the molecular mechanism of sudden coronary death (SCD). Rat models of atherosclerotic death (ASD), coronary atherosclerosis (AS), and acute myocardial ischemia (AMI) and sham groups were established via the gavage of high-fat emulsion and left coronary artery ligation. The myocardium was collected, and transcriptome sequencing was performed. Differentially expressed miRNAs (DEmiRNAs) were identified using edeR software. The target genes were predicted using TargetScan, and functional enrichment analysis was performed via KEGG. Then, an miRNA–mRNA interaction network was constructed using Cytoscape. The key miRNAs with biomarker potential were identified using LASSO regression. A total of 217, 224, and 86 DEmiRNAs were identified in the ASD, AS, and AMI groups compared with the sham group, respectively. The Ras and Rap1 pathways were mainly expressed in ASD. The β-alanine and sphingolipid metabolisms were expressed in AMI. Finally, miR-106b, miR-195, miR-33, miR-652, miR-466b, and miR-6321 were identified as biomarkers of ASD. MiR-205, miR-877, miR-325, and miR-344b were identified as biomarkers of AMI. miR542-Atg12 was involved in the RIG-I-like receptor signaling pathway, miR6328-Gstz1 was involved in tyrosine metabolism, and miR483-Dusp5 was involved in the MAPK signaling pathway. This study provides a reference for the identification of SCD in forensic pathology. Full article

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

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21 pages, 1102 KB

Open AccessReview

Research Progress on Signalling Pathways Related to Sepsis-Associated Acute Kidney Injury in Children

by Zhenkun Zhang, Meijun Sheng, Yiyao Bao and Chao Tang

Curr. Issues Mol. Biol. 2025, 47(11), 888; https://doi.org/10.3390/cimb47110888 (registering DOI) - 27 Oct 2025

Abstract

Sepsis-associated acute kidney injury (SA-AKI) is a prevalent and life-threatening complication in critically ill children, contributing to high mortality rates (up to 30%) and long-term renal dysfunction in pediatric intensive care units. This review synthesizes recent advances in the signalling pathways underlying SA-AKI, [...] Read more.

Sepsis-associated acute kidney injury (SA-AKI) is a prevalent and life-threatening complication in critically ill children, contributing to high mortality rates (up to 30%) and long-term renal dysfunction in pediatric intensive care units. This review synthesizes recent advances in the signalling pathways underlying SA-AKI, emphasizing pediatric-specific mechanisms, biomarkers, and therapeutic targets. This review covers inflammatory cascades via TLR/NF-κB leading to cytokine storms (IL-6, TNF-α); apoptosis and necrosis involving mitochondrial Bcl-2 dysregulation and OLFM4; and emerging processes like pyroptosis (NF-κB-mediated), metabolic reprogramming (choline deficiency and Nrf2-mitophagy), and novel routes such as cGAS-STING and TGF-β signalling. Biomarkers like urinary OLFM4, DKK3, NGAL, and serum suPAR, alanine, and Penkid enable early diagnosis and risk stratification, with models like PERSEVERE-II enhancing prognostic accuracy. Therapeutic strategies include fluid optimization, renal replacement therapies (CRRT, SLED-f), and pathway-targeted interventions such as choline supplementation, oXiris for cytokine removal, Humanin for immunomodulation, and investigational cGAS-STING inhibitors. Despite progress, challenges persist in translating animal models to pediatric trials and addressing heterogeneity. Integrating multi-omics and precision medicine holds promise for improving outcomes, underscoring the need for multicenter studies in children. Full article

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

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16 pages, 1200 KB

Open AccessReview

HMGB1 and Its Signaling Pathway in Osteosarcoma: Current Advances in Targeted Therapy

by Zhuosheng Liu, Fucai Wang, Zhihan Zhou, Mei Wu, Qinghua Huang, Xinpeng Jiang, Xuan Wen and Liuting Ye

Curr. Issues Mol. Biol. 2025, 47(11), 887; https://doi.org/10.3390/cimb47110887 (registering DOI) - 27 Oct 2025

Abstract

This article reviews the research progress for high-mobility group protein B1 (HMGB1) and its signaling pathway in osteosarcoma (OS) and discusses its application potential in targeted therapy. A large number of domestic and foreign studies were reviewed to summarize the research results on [...] Read more.

This article reviews the research progress for high-mobility group protein B1 (HMGB1) and its signaling pathway in osteosarcoma (OS) and discusses its application potential in targeted therapy. A large number of domestic and foreign studies were reviewed to summarize the research results on the the biological function, signal pathway regulation mechanism, and intervention strategy of HMGB1 in recent years. HMGB1 promotes OS cell proliferation, invasion, and immune escape by activating RAGE, TLR4, and downstream MAPK, NF-κB, and PI3K/AKT signaling pathways. Interfering with HMGB1 or its signaling axis shows good antitumor potential in in vitro and in vivo models, but clinical transformation is still limited by its dual biological effects and tumor heterogeneity. HMGB1 and its related signaling pathways are important targets for the treatment of osteosarcoma. In the future, the development of a multi-channel combined intervention and efficient delivery system will provide a new direction for improving the therapeutic effect. Full article

(This article belongs to the Section Molecular Medicine)

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26 pages, 1170 KB

Open AccessReview

Cellular and Molecular Pathways in Diabetes-Associated Heart Failure: Emerging Mechanistic Insights and Therapeutic Opportunities

by Nikolaos Ktenopoulos, Lilian Anagnostopoulou, Anastasios Apostolos, Panagiotis Iliakis, Paschalis Karakasis, Nikias Milaras, Panagiotis Theofilis, Christos Fragoulis, Maria Drakopoulou, Andreas Synetos, George Latsios, Konstantinos Tsioufis and Konstantinos Toutouzas

Curr. Issues Mol. Biol. 2025, 47(11), 886; https://doi.org/10.3390/cimb47110886 (registering DOI) - 26 Oct 2025

Abstract

Diabetes mellitus (DM) is a global health challenge that contributes to numerous complications. As a chronic metabolic disorder, DM leads to persistent microvascular and macrovascular damage, ultimately impairing the function of multiple organ systems. Cardiovascular diseases (CVD), including heart failure (HF), are among [...] Read more.

Diabetes mellitus (DM) is a global health challenge that contributes to numerous complications. As a chronic metabolic disorder, DM leads to persistent microvascular and macrovascular damage, ultimately impairing the function of multiple organ systems. Cardiovascular diseases (CVD), including heart failure (HF), are among the most serious diabetes-related outcomes, accounting for substantial morbidity and mortality worldwide. Traditionally, diabetic HF has been attributed to coexisting conditions such as hypertensive heart disease or coronary artery disease. However, a high prevalence of HF is observed in individuals with DM even in the absence of these comorbidities. In recent years, the phenomenon of diabetes-induced HF has attracted considerable scientific interest. Gaining insight into the mechanisms by which diabetes elevates HF risk and drives key molecular and cellular alterations is essential for developing effective strategies to prevent or reverse these pathological changes. This review consolidates current evidence and recent advances regarding the cellular and molecular pathways underlying diabetes-related HF. Full article

(This article belongs to the Section Molecular Medicine)

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34 pages, 5331 KB

Open AccessReview

Inflammation, Apoptosis, and Fibrosis in Diabetic Nephropathy: Molecular Crosstalk in Proximal Tubular Epithelial Cells and Therapeutic Implications

by Xuanke Liu, Chunjiang Zhang, Yanjie Fu, Linlin Xie, Yijing Kong and Xiaoping Yang

Curr. Issues Mol. Biol. 2025, 47(11), 885; https://doi.org/10.3390/cimb47110885 (registering DOI) - 24 Oct 2025

Abstract

Diabetic nephropathy (DN) remains the leading cause of end-stage renal disease worldwide, with proximal tubular epithelial cells (PTECs) playing a central role in its pathogenesis. Under hyperglycemic conditions, PTECs drive a pathological triad of inflammation, apoptosis, and fibrosis. Recent advances reveal that these [...] Read more.

Diabetic nephropathy (DN) remains the leading cause of end-stage renal disease worldwide, with proximal tubular epithelial cells (PTECs) playing a central role in its pathogenesis. Under hyperglycemic conditions, PTECs drive a pathological triad of inflammation, apoptosis, and fibrosis. Recent advances reveal that these processes interact synergistically to form a self-perpetuating vicious cycle, rather than operating in isolation. This review systematically elucidates the molecular mechanisms underlying this crosstalk in PTECs. Hyperglycemia induces reactive oxygen species (ROS) overproduction, advanced glycation end products (AGEs) accumulation, and endoplasmic reticulum stress (ERS), which collectively activate key inflammatory pathways (NF-κB, NLRP3, cGAS-STING). The resulting inflammatory milieu triggers apoptosis via death receptor and mitochondrial pathways, while apoptotic cells release damage-associated molecular patterns (DAMPs) that further amplify inflammation. Concurrently, fibrogenic signaling (TGF-β1/Smad, Hippo-YAP/TAZ) promotes epithelial–mesenchymal transition (EMT) and extracellular matrix (ECM) deposition. Crucially, the resulting fibrotic microenvironment reciprocally exacerbates inflammation and apoptosis through mechanical stress and hypoxia. Quantitative data from preclinical and clinical studies are integrated to underscore the magnitude of these effects. Current therapeutic strategies are evolving toward multi-target interventions against this pathological network. We contrast the paradigm of monotargeted agents (e.g., Finerenone, SGLT2 inhibitors), which offer high specificity, with that of multi-targeted natural product-based formulations (e.g., Huangkui capsule, Astragaloside IV), which provide synergistic multi-pathway modulation. Emerging approaches (metabolic reprogramming, epigenetic regulation, mechanobiological signaling) hold promise for reversing fibrosis. Future directions include leveraging single-cell technologies to decipher PTEC heterogeneity and developing kidney-targeted drug delivery systems. We conclude that disrupting the inflammation–apoptosis–fibrosis vicious cycle in PTECs is central to developing next-generation therapies for DN. Full article

(This article belongs to the Special Issue Autophagy and the Ubiquitin–Proteasome System: Regulators of Protein Homeostasis, Cell Death, and Disease Pathogenesis)

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24 pages, 1173 KB

Open AccessArticle

A Retrospective Assessment of Changes in Stroke Risk-Related Biomarkers in Individuals with Prediabetes from Durban, South Africa: Preliminary Findings

by Yerushka Naicker and Andile Khathi

Curr. Issues Mol. Biol. 2025, 47(11), 884; https://doi.org/10.3390/cimb47110884 (registering DOI) - 24 Oct 2025

Abstract

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that significantly increases the risk of stroke, with prediabetes serving as an intermediate stage marked by similar pathophysiological mechanisms such as inflammation and vascular dysfunction. This study investigated the relationship between prediabetes and [...] Read more.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that significantly increases the risk of stroke, with prediabetes serving as an intermediate stage marked by similar pathophysiological mechanisms such as inflammation and vascular dysfunction. This study investigated the relationship between prediabetes and stroke-related biomarkers in individuals aged 25–45 years in Durban, South Africa. After obtaining ethical approval, a retrospective analysis was performed on blood samples from 100 participants recruited from King Edward Hospital and Inkosi Albert Luthuli Central Hospital. Participants were classified as non-prediabetic (n = 30), prediabetic (n = 35), or type 2 diabetic (n = 35) according to ADA criteria. Plasma concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen, D-dimer, calcium binding protein (S100B), glial fibrillary acidic protein (GFAP), and neuron-specific enolase (NSE) were measured using enzyme-linked immunosorbent assay (ELISA). It is important to note that none of the participants had confirmed stroke events; these biomarkers were assessed as surrogate indicators of stroke risk. Statistical analyses included one-way ANOVA with Tukey–Kramer tests and Pearson’s correlations. Biomarker concentrations were significantly elevated in prediabetic individuals compared to non-prediabetic controls, with levels further increasing in T2DM. Strong positive correlations were observed between S100B and both HbA1c (r = 0.75, p < 0.0001) and fasting glucose (r = 0.75, p < 0.0001). These findings suggest that inflammatory, coagulation, and neurovascular biomarkers, particularly S100B, may indicate early stroke risk in prediabetes. Further investigation into these biomarkers could improve early detection strategies and stroke prevention efforts in at-risk populations. Full article

(This article belongs to the Special Issue Cerebrovascular Diseases: From Pathogenesis to Treatment)

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16 pages, 6424 KB

Open AccessArticle

CNPY3 Promotes Human Breast Cancer Progression and Metastasis via Modulation of the Tumor Microenvironment

by Xiaofeng Duan, Ran Zhao, Shaoli Sun, Beichu Guo, Zihai Li and Bei Liu

Curr. Issues Mol. Biol. 2025, 47(11), 883; https://doi.org/10.3390/cimb47110883 - 24 Oct 2025

Abstract

Canopy FGF signaling regulator 3 (CNPY3) is a cochaperone of the molecular chaperone GRP94. CNPY3 is critical for the post-translational maturation of toll-like receptors and for regulating inflammasome signaling. However, the role of CNPY3 in cancer development and progression is still not fully [...] Read more.

Canopy FGF signaling regulator 3 (CNPY3) is a cochaperone of the molecular chaperone GRP94. CNPY3 is critical for the post-translational maturation of toll-like receptors and for regulating inflammasome signaling. However, the role of CNPY3 in cancer development and progression is still not fully understood. In this study, we aimed to investigate the role of CNPY3 in human breast cancer progression and metastasis. We used genomic and clinical information from multiple databases to profile CNPY3 and GRP94 in human cancers. We found that CNPY3 and GRP94 were elevated in human breast cancers compared to normal tissue. Higher expression of CNPY3 correlated with cancer progression and poor clinical outcomes in breast cancers. We confirmed these findings using a human breast cancer tissue array. We silenced CNPY3 in human breast cancer cells using a CRISPR/Cas9 system. For the first time, we found that deletion of CNPY3 significantly reduced tumor growth and metastasis in vitro and in vivo. Additionally, network and enrichment analyses revealed that changes in the unfolded protein response pathway and immune-related genes were significantly dependent on alterations in CNPY3 and GRP94. This study suggests that CNPY3 is a potential biomarker and novel therapeutic target for cancers. Full article

(This article belongs to the Special Issue Tumorigenesis and Tumor Microenvironment)

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17 pages, 2373 KB

Open AccessArticle

Genome-Wide Identification, Phylogeny and Expression Analysis of the Magnesium Release Gene Family in Wheat (Triticum aestivum L.)

by Yuanxue Chen, Weiwei Zhang, Fengjuan Zhao, Guolan Liu, Deyong Zhao, Jikun Xu, Xin Wang, Xuehui Zong, Jingmin Zhang, Xiaoqing Ji, Jingyi Ma, Shuaipeng Zhao and Jian Li

Curr. Issues Mol. Biol. 2025, 47(11), 882; https://doi.org/10.3390/cimb47110882 (registering DOI) - 23 Oct 2025

Abstract

Magnesium (Mg) release (MGR) proteins play a crucial role in maintaining Mg²⁺ homeostasis in plant cells. However, MGR family genes have not yet been explored in crops. This study identified the wheat MGR (TaMGR) family members via BlastP alignment. A total of [...] Read more.

Magnesium (Mg) release (MGR) proteins play a crucial role in maintaining Mg²⁺ homeostasis in plant cells. However, MGR family genes have not yet been explored in crops. This study identified the wheat MGR (TaMGR) family members via BlastP alignment. A total of 15 MGR genes were mapped to 12 chromosomes. Cis-element prediction in the promoter region revealed that the ABA-responsive element (ABRE) was 100% conserved among all family members. Collinearity analysis indicates that MGR genes in monocot plants may have higher conservation compared to dicot plants. Expression profiling analyses uncovered the expression patterns of TaMGR genes across diverse tissues and under various stresses. Our results demonstrated that TaMGR5D and TaMGR5A.2 were significantly induced by both powdery mildew and stripe rust pathogen infections, whereas TaMGR4A transcript levels were upregulated in response to drought, heat and their combined stress. These findings indicate that TaMGRs may contribute coordinately to the regulation of wheat growth and development as well as adaptive responses to adverse conditions through member-specific expression patterns. This study systematically identified and analyzed the evolution and expression regulation characteristics of TaMGRs, providing a theoretical basis for in-depth research on the functional mechanisms of the TaMGRs and for improving the Mg use efficiency and stress adaptability of wheat via molecular approaches. Full article

(This article belongs to the Section Molecular Plant Sciences)

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18 pages, 4090 KB

Open AccessArticle

Expression of TIM-3 and Gal-9 Immune Checkpoints in Chronic Lymphocytic Leukemia: The Potential Role of Interleukin-27

by Ewelina Wędrowska, Tomasz Wandtke, Bartosz Ulaszewski, Edyta Cichocka, Robert Dębski, Piotr Kopiński, Jan Styczyński and Grzegorz Przybylski

Curr. Issues Mol. Biol. 2025, 47(11), 881; https://doi.org/10.3390/cimb47110881 - 23 Oct 2025

Abstract

Background: Chronic lymphocytic leukemia (CLL) is characterized by malignant B lymphocyte accumulation and progressive immune dysfunction. The immune checkpoint molecule TIM-3 and its ligand galectin-9 (Gal-9) contribute to T cell exhaustion, impairing anti-tumour immunity. Interleukin-27 (IL-27) has pleiotropic immunomodulatory properties, but its impact [...] Read more.

Background: Chronic lymphocytic leukemia (CLL) is characterized by malignant B lymphocyte accumulation and progressive immune dysfunction. The immune checkpoint molecule TIM-3 and its ligand galectin-9 (Gal-9) contribute to T cell exhaustion, impairing anti-tumour immunity. Interleukin-27 (IL-27) has pleiotropic immunomodulatory properties, but its impact on TIM-3 and Gal-9 expression in CLL remains unclear. Methods: Peripheral blood mononuclear cells (PBMCs) from 20 treatment-naive CLL patients were cultured with or without IL-27 (100 ng/mL) for 72 h. Flow cytometry assessed TIM-3 and Gal-9 expression on CD4⁺, CD8⁺, and CD19⁺ cells. Results: IL-27 stimulation significantly increased TIM-3 expression on CD8⁺ T cells (2.18 ± 0.32% vs. 3.09 ± 0.49%, p = 0.009), a hallmark of T cell exhaustion. IL-27 also modestly increased intracellular Gal-9 levels in total lymphocytes (93.91 ± 1.17% vs. 96.55 ± 0.67%, p = 0.005). Additionally, IL-27 reduced CD4⁺ T cell proportions (26.71 ± 4.19% vs. 22.01 ± 3.23%, p = 0.010). Although numerically modest, these changes may be biologically pertinent in the context of checkpoint-mediated CD8⁺ T-cell exhaustion. Conclusions: IL-27 may enhance immunosuppressive mechanisms in CLL by modulating immune checkpoint expression, potentially contributing to disease progression. These ex vivo findings in PBMCs from CLL patients indicate the IL-27-associated modulation of checkpoint expression under the conditions tested. In the absence of parallel healthy-donor controls, CLL specificity cannot be established in this study. Full article

(This article belongs to the Section Molecular Medicine)

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14 pages, 1350 KB

Open AccessArticle

Whole Exome Sequencing for the Identification of Mutations in Bone Marrow CD34+Cells in Hodgkin Lymphoma

by Phan Thi Hoai Trang, Do Thi Trang, Pham Thi Huong, Pham Viet Nhat, Mentor Sopjani, Nguyen Hoang Giang, Nguyen Xuan Canh, Nguyen Van Giang, Nguyen Trung Nam, Nguyen Ba Vuong, Vu Duc Binh and Nguyen Thi Xuan

Curr. Issues Mol. Biol. 2025, 47(11), 880; https://doi.org/10.3390/cimb47110880 - 23 Oct 2025

Abstract

Background: Classical Hodgkin lymphoma (cHL) is a rare B-cell malignant neoplasm, characterized by the presence of rare mononucleated Hodgkin and multinucleated Reed–Sternberg cells (HRS). CD34+ cells are highly expressed on lymphoma stem cells in bone marrow (BM). Little is known about gene mutations [...] Read more.

Background: Classical Hodgkin lymphoma (cHL) is a rare B-cell malignant neoplasm, characterized by the presence of rare mononucleated Hodgkin and multinucleated Reed–Sternberg cells (HRS). CD34+ cells are highly expressed on lymphoma stem cells in bone marrow (BM). Little is known about gene mutations in BM CD34+ cells of cHL. In this study, whole exome sequencing (WES) was performed and high-frequency mutation genes were examined through their expression levels. Materials and Methods: The influence of the variants on protein function was predicted with in silico tools or public databases. Gene expression levels were determined by quantitative real-time PCR. Results: WES assay from BM CD34+ cells in thirty cHL patients revealed that three variants were detected in known cHL-associated genes, including NCF1 (13.33%), MMP9 (3.33%), and VDR (3.33%). We also observed other candidate genes including CNN2 rs77830704 (76.67%), CNN2 rs78386506 (63.33%), MUC4 p.Y3278_Q3209Del (66.67%), MUC4 p.P1076_P1124Del (33.33%), MUC4 rs748236754 (26.67%), MUC4 p.P1609Ins (23.33%), MUC4 rs748705487 (20%), MUC4 p.P4121_P4137Del (16.67%), MTSS2 rs531163149 (13.33%), KMT2C rs201834857 (20%), HAVCR2 rs184868814 (16.67%), and TCF19 rs541001159 (13.33%). Moreover, the low levels of MUC4 were associated with an increase in neutrophil-to-lymphocyte ratio and the low CNN2 expression group had higher levels of LDH, suggesting that the low expressions of CNN2 and MUC4 might be important risk factors for poor prognosis in cHL. Conclusions: WES revealed significantly mutated genes, most of which were associated with the physiological activation of lymphoma cells. This finding contributed to the identification of novel gene variants that might impact on the function of BM CD34+ cells in cHL patients. Full article

(This article belongs to the Section Molecular Medicine)

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16 pages, 1332 KB

Open AccessArticle

Development and Evaluation of Six Novel Recombinant GRA Proteins in Serodiagnosis of Human Toxoplasmosis

by Karolina Sołowińska and Lucyna Holec-Gąsior

Curr. Issues Mol. Biol. 2025, 47(11), 879; https://doi.org/10.3390/cimb47110879 - 23 Oct 2025

Abstract

Toxoplasma gondii is a globally distributed protozoan parasite, and reliable serodiagnosis is essential for effective management of toxoplasmosis. Conventional assays rely on tachyzoite lysate antigen (TLA), which suffers from limited standardization and reproducibility. In this study, immunodominant fragments of six dense granule proteins—GRA29, [...] Read more.

Toxoplasma gondii is a globally distributed protozoan parasite, and reliable serodiagnosis is essential for effective management of toxoplasmosis. Conventional assays rely on tachyzoite lysate antigen (TLA), which suffers from limited standardization and reproducibility. In this study, immunodominant fragments of six dense granule proteins—GRA29, GRA35, GRA36, GRA45, GRA54, and GRA64—were expressed in Escherichia coli, purified, and evaluated as candidate antigens in IgG ELISAs using human sera. This study represents the first assessment of their diagnostic utility. Initial screening identified GRA29, GRA45, and GRA54 as promising candidates, with AUC values of 0.9983, 0.8507, and 0.9323, respectively, while GRA35-, GRA36-, and GRA64-based ELISA showed poor discrimination between seropositive and seronegative samples. Extended evaluation of GRA29-based assay with a larger serum panel (n = 286) confirmed excellent diagnostic performance, yielding an AUC of 0.9942 and higher sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) compared with TLA-ELISA. A comparative analysis revealed that GRA29 produced stronger reactivity in positive sera and lower background in negatives. These findings highlight GRA29 as a promising recombinant antigen for the serodiagnosis of human toxoplasmosis and a potential standardized alternative to TLA. Full article

(This article belongs to the Section Molecular Microbiology)

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22 pages, 709 KB

Open AccessReview

Recombinant Oncolytic Viruses: Hexagonal Warriors in the Field of Solid Tumor Immunotherapy

by Cong Zhang and Qian Sun

Curr. Issues Mol. Biol. 2025, 47(11), 878; https://doi.org/10.3390/cimb47110878 - 23 Oct 2025

Abstract

In the past decade, research on recombinant oncolytic viral agents in the treatment of solid tumors has evolved from the initial stage of simple genetic engineering to the current stage of multiple pipelines of parallel clinical application and combination therapy. Compared with T-VEC, [...] Read more.

In the past decade, research on recombinant oncolytic viral agents in the treatment of solid tumors has evolved from the initial stage of simple genetic engineering to the current stage of multiple pipelines of parallel clinical application and combination therapy. Compared with T-VEC, the classical therapeutic agent that only expresses GM-CSF, which was approved in 2015, most new oncolytic virus designs include diverse gene constructs to reduce toxic effects, enhance multiple antitumor immunity, avoid immune clearance, or enhance tumor targeting. The single route of administration that activates the inflammatory tumor immune microenvironment by intratumoral injection is no longer sufficient to meet the treatment needs of refractory solid tumors. In this review, we illustrated the construction patterns of typical recombinant oncolytic viral agents and their latest clinical trial progress. Secondly, we summarized the underlying mechanisms of the combined application of antiviral and antitumor immunity in the field of solid tumor immunotherapy. Finally, we explored the feasibility of the intravenous application of oncolytic viruses and their future development directions. We believe that the diversified treatment design of oncolytic viruses will bring more surprises to the immunotherapy of refractory tumors. Full article

(This article belongs to the Topic Antibody-Mediated Therapy and Other Emerging Therapies in Cancer Treatment)

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19 pages, 2455 KB

Open AccessArticle

Genetic Trends in General Combining Ability for Maize Yield-Related Traits in Northeast China

by Haochen Wang, Xiaocong Zhang, Jianfeng Weng, Mingshun Li, Zhuanfang Hao, Degui Zhang, Hongjun Yong, Jienan Han, Zhiqiang Zhou and Xinhai Li

Curr. Issues Mol. Biol. 2025, 47(11), 877; https://doi.org/10.3390/cimb47110877 - 23 Oct 2025

Abstract

Maize (Zea mays L.) is the most extensively cultivated food crop in China, and current studies on maize general combining ability (GCA) focus primarily on the genetic basis of traits. However, the dynamic trends and underlying genetic loci associated with GCA for [...] Read more.

Maize (Zea mays L.) is the most extensively cultivated food crop in China, and current studies on maize general combining ability (GCA) focus primarily on the genetic basis of traits. However, the dynamic trends and underlying genetic loci associated with GCA for yield-related traits during breeding remain underexplored. This study was designed to investigate the changing trends of the general combining ability (GCA) and the frequency of elite alleles among 218 major maize inbred lines from Northeast China, spanning the 1970s to the 2010s. PH6WC and PH4CV were used as testers to develop 436 hybrid combinations via the North Carolina design II (NCII) method, and these combinations were evaluated across three environments. We further analyzed the combining ability (particularly the GCA) of 16 yield-related traits and their dynamic trends during breeding, grouped into three age periods (AGE1: 1960s–1970s; AGE2: 1980s–1990s; AGE3: 2000s–2010s). We also screened for genetic loci associated with the GCA effects of these traits. Results show that breeding selection significantly affected the GCA of six yield-related traits (ear length (EL), tassel branch number (TBN), tassel main axis length (TL), kernel length (KL), stem diameter (SDR), and hundred kernel weight (HKW)). Specifically, the mean TBN_GCA value decreased from 2.51 in AGE1 to −1.28 in AGE3, and the mean HKW_GCA increased from −1.58 in AGE1 to 0.36 in AGE3. Yield per plant GCA (YPP_GCA) was positively correlated with the GCA values of EL, ear diameter (ED), kernel row number (KRN), kernel number per row (KNPR), and HKW. Association analysis identified 38 single nucleotide polymorphisms (SNP_S) related to GCA. The T/T alleles for TBN were absent in AGE1, emerged in AGE2 (1980s–1990s), and persisted in AGE3—consistent with the decreasing trend of TBN_GCA from AGE1 to AGE3. For HKW, the A/A alleles not only exhibited higher GCA (effectively improving the HKW_GCA of inbred lines) but also showed an 11% increase in allelic frequency from AGE1 to AGE3. Taken together, these results suggest that the accumulation of elite alleles is the primary factor driving the GCA improvement during maize breeding in Northeast China. Full article

(This article belongs to the Special Issue Advances in Multi-Omics for Functional Genomics Studies and Molecular Breeding, 2nd Edition)

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