Current Issues in Molecular Biology

16 pages, 3716 KiB

Open AccessArticle

Genome-Wide Analysis of Oxidosqualene Cyclase Genes in Artemisia annua: Evolution, Expression, and Potential Roles in Triterpenoid Biosynthesis

by Changfeng Guo, Si Xu and Xiaoyun Guo

Curr. Issues Mol. Biol. 2025, 47(7), 545; https://doi.org/10.3390/cimb47070545 - 14 Jul 2025

Abstract

Plant triterpenoids are structurally diverse specialized metabolites with significant ecological, medicinal, and agricultural importance. Oxidosqualene cyclases (OSCs) catalyze the crucial cyclization step in triterpenoid biosynthesis, generating the fundamental carbon skeletons that determine their structural diversity and biological functions. Genome-wide identification of OSC genes [...] Read more.

Plant triterpenoids are structurally diverse specialized metabolites with significant ecological, medicinal, and agricultural importance. Oxidosqualene cyclases (OSCs) catalyze the crucial cyclization step in triterpenoid biosynthesis, generating the fundamental carbon skeletons that determine their structural diversity and biological functions. Genome-wide identification of OSC genes was performed using bioinformatics tools, including HMMER and BLASTP, followed by phylogenetic analysis, gene structure analysis, conserved domain and motifs identification, cis-regulatory element prediction, protein–protein interaction analysis, and expression profiling using publicly available transcriptome data from UV-B treated A. annua six-week-old seedlings. We identified 24 AaOSC genes, classified into CAS, LAS, LUS, and unknown subfamilies. Phylogenetic analysis revealed evolutionary relationships with OSCs from other plant species. Gene structure analysis showed variations in exon–intron organization. Promoter analysis identified cis-regulatory elements related to light responsiveness, plant growth and development, hormone signaling, and stress response. Expression profiling revealed differential expression patterns of AaOSC genes under UV-B irradiation. This genome-wide characterization provides insights into the evolution and functional diversification of the OSC gene family in A. annua. The identified AaOSC genes and their regulatory elements lay the foundation for future studies aimed at manipulating triterpenoid biosynthesis for medicinal and biotechnological applications, particularly focusing on enhancing stress tolerance and artemisinin production. Full article

(This article belongs to the Special Issue Functional Genomics and Comparative Genomics Analysis in Plants, 3rd Edition)

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15 pages, 2126 KiB

Open AccessReview

Prognostic Value of the Immunohistochemical Detection of Cellular Components of the Tumor Microenvironment in Oral Squamous Cell Carcinoma: A Systematic Review

by Hannah Gil de Farias Morais, Caroline Fernandes da Costa, Maurília Raquel de Souto Medeiros, Bárbara de Assis Araújo, Everton Freitas de Morais, Ricardo D. Coletta and Roseana de Almeida Freitas

Curr. Issues Mol. Biol. 2025, 47(7), 544; https://doi.org/10.3390/cimb47070544 - 12 Jul 2025

Abstract

This study aims to investigate the prognostic impact of cellular components of the tumor microenvironment (TME), analyzed through immunohistochemistry, in oral squamous cell carcinoma (OSCC). This review was conducted following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). [...] Read more.

This study aims to investigate the prognostic impact of cellular components of the tumor microenvironment (TME), analyzed through immunohistochemistry, in oral squamous cell carcinoma (OSCC). This review was conducted following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Searches were performed in EMBASE, Medline/PubMed, Cochrane Collaboration Library, Web of Science, ScienceDirect, Scopus, and Google Scholar. After applying the study criteria, 59 articles were included, involving the analysis of cancer-associated fibroblasts (CAFs), immune cells, and endothelial cells. It was found that TME rich in α-SMA-positive CAFs, tumor-associated macrophages, and dendritic cells contribute to the invasion and progression of OSCC, resulting in a poorer prognosis. In contrast, the presence of high amounts of NK CD57⁺ cells, CD8⁺/CD45RO⁺ T cells, and PNAd⁺ endothelial cells are associated with anti-tumor immune responses in OSCC and improved survival rates. CD3⁺ and CD4⁺ T cells, Treg cells, B cells, and mast cells have shown little to no evidence of prognostic utility. Several stromal components of TME were found to have a strong impact on the aggressiveness of OSCC, reaffirming the potential use of these biomarkers as prognostic tools and therapeutic targets. Full article

(This article belongs to the Special Issue Oral Cancer: Prophylaxis, Etiopathogenesis and Treatment, 2nd Edition)

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22 pages, 12756 KiB

Open AccessArticle

The Antidiabetic Mechanisms of Cinnamon Extract: Insights from Network Pharmacology, Gut Microbiota, and Metabolites

by Rong Wang, Kuan Yang, Xuefeng Liu, Yiye Zhang, Yunmei Chen, Nana Wang, Lili Yu, Shaojing Liu, Yaqi Hu and Bei Qin

Curr. Issues Mol. Biol. 2025, 47(7), 543; https://doi.org/10.3390/cimb47070543 - 12 Jul 2025

Abstract

The progression of type 2 diabetes mellitus (T2DM) is shaped by a multifaceted interplay among genetic, behavioral, and environmental factors, alongside gut dysbiosis. Cinnamon, being abundant in polyphenols and flavonoids, shows significant antioxidant effects. Studies have substantiated that cinnamon contributes to the management [...] Read more.

The progression of type 2 diabetes mellitus (T2DM) is shaped by a multifaceted interplay among genetic, behavioral, and environmental factors, alongside gut dysbiosis. Cinnamon, being abundant in polyphenols and flavonoids, shows significant antioxidant effects. Studies have substantiated that cinnamon contributes to the management of glucose and lipid metabolism. However, the anti-diabetic efficacy of cinnamon is not completely understood. The objective of this research was to clarify the anti-diabetic mechanism associated with cinnamon extract through a combination of chemical profiling, network pharmacology, and in vivo investigations. The results indicated that 32 chemical ingredients, including quercetin, were identified through UPLC-Q-TOF-MS. Network pharmacology revealed that 471 targets related to 14 compounds were screened. The analysis of GO enrichment revealed that the primary pathways were notably enhanced in the metabolism of insulin and glucose. In vivo analyses showed that cinnamon could effectively alleviate hyperglycemia, insulin resistance, and lipid metabolism abnormalities via increased relative abundance of Akkermansia and Ligilactobacillus at the genus level and a decreased Firmicutes/Bacteroidetes ratio at the phylum level. Moreover, cinnamon reduced the serum levels of lipopolysaccharide (LPS) and proinflammatory cytokines (IL-6 and TNF-α) and significantly increased the colon Zonula occludens-1 (ZO-1) and occludin protein levels. It was also observed that cinnamon improved the fecal SCFA levels (acetic, propionic, butyric, valeric and caproic acid), while also modifying the bile acid (BA) profile and increasing the conjugated-to-unconjugated BA ratio. The Western blotting analysis further demonstrated that cinnamon activated intestinal FXR/FGF15 and hepatic PI3K/AKT signaling pathways. In summary, the finding confirmed that cinnamon ameliorated glucose and lipid metabolism disorders by safeguarding the intestinal barrier and modulating the gut microbiota and metabolites, thereby activating intestinal FXR/FGF15 and hepatic PI3K/AKT signaling pathways. Full article

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

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21 pages, 5459 KiB

Open AccessArticle

NAC Gene Family in Lagerstroemia indica: Genome-Wide Identification, Characterization, Expression Analysis, and Key Regulators Involved in Anthocyanin Biosynthesis

by Zilong Gao, Zhuomei Chen, Jinfeng Wang and Weixin Liu

Curr. Issues Mol. Biol. 2025, 47(7), 542; https://doi.org/10.3390/cimb47070542 - 11 Jul 2025

Abstract

NAC (NAM, ATAF1/2, CUC1/2) is a plant-specific transcription factor (TF) family that plays important roles in various physiological and biochemical processes of plants. However, the NAC gene family in Lagerstroemia indica and its role in anthocyanin metabolism are still unexplored. In our study, [...] Read more.

NAC (NAM, ATAF1/2, CUC1/2) is a plant-specific transcription factor (TF) family that plays important roles in various physiological and biochemical processes of plants. However, the NAC gene family in Lagerstroemia indica and its role in anthocyanin metabolism are still unexplored. In our study, a total of 167 NACs were identified in the L. indica genome via genome-wide analysis and bioinformatics techniques. Amino acid sequence analysis showed that all 167 NAC proteins contained a conserved NAM domain. This domain primarily comprised random coils, extended strands, and alpha helices. Most NACs were found on the nucleus and dispersed over 23 of the 24 plant chromosomes. Based on phylogenetic analysis, the NACs can be categorized into ten subgroups. Furthermore, the promoter homeotropic elements predicted the cis-acting elements in the promoters of these genes related to hormones, development, environmental stress response, and other related responses, demonstrating the diverse regulatory mechanisms underlying gene functions. In addition, a co-expression network was established through RNA sequencing. This network helped identify seven key LiNACs, genes related to anthocyanin expression (CHS) and transcription factors (MYB and bHLH). To identify potential anthocyanin regulatory factors present in L. indica petals, protein interaction prediction was performed, which revealed that LiNACs might participate in anthocyanin regulation by interacting with other proteins, such as MYB, ABF, ABI, bZIP, MYC, etc. Our results provided novel insights and could help in the functional identification of LiNACs in L. indica and the regulation of anthocyanin synthesis. Full article

(This article belongs to the Special Issue Molecular Breeding and Genetics Research in Plants, 2nd Edition)

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16 pages, 2901 KiB

Open AccessArticle

Analysis of Pharmacological Activities and Mechanisms of Essential Oil in Flowers of Citrus grandis ‘Tomentosa’ by GC-MS/MS and Network Pharmacology

by Danxi Yan, Shuyi Wen, Mingxia Chen, Jinlan Huang, Guihao Zhang, Renkai Li, Jiamin Lu, Zhongxuan Yao, Fei Gao and Jieshu You

Curr. Issues Mol. Biol. 2025, 47(7), 541; https://doi.org/10.3390/cimb47070541 - 11 Jul 2025

Abstract

According to our research, the flowers from Citrus grandis ‘Tomentosa’ contain rich biologically active essential oil components, but the chemical components and relative pharmacological properties have not been systematically studied. Therefore, the study aimed to identify the essential oil components by GC-MS/MS and [...] Read more.

According to our research, the flowers from Citrus grandis ‘Tomentosa’ contain rich biologically active essential oil components, but the chemical components and relative pharmacological properties have not been systematically studied. Therefore, the study aimed to identify the essential oil components by GC-MS/MS and explore the pharmacological activity and mechanism of these essential oil components by a network pharmacology approach. Finally, GC-MS/MS analysis identified 43 essential oil components, which corresponded to 739 potential targets. GO analysis results showed that 12, 18, and 12 entries were related to biological processes, cellular components, and molecular functions, respectively. A total of 120 pathways were obtained based on KEGG analysis, of which the most important was the adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway. The “active component–target–disease” network further demonstrated these essential oil components’ potential efficacy against pain, tumors, neuropsychiatric diseases, eye diseases, and respiratory diseases, which were highly related to PPARA, GABRA1, PTGS2, and SLC6A2. Experimental validation confirmed that β-caryophyllene, a major constituent, dose-dependently inhibited the proliferation of HT29 and MCF-7 cells (0–320 μM). This study provides a reliable basis for elucidating the pharmacological activity of the essential oil components and related mechanisms, which is beneficial to the comprehensive utilization and development of Citrus grandis ‘Tomentosa’. Full article

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

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29 pages, 538 KiB

Open AccessReview

Dynamic Rendition of Adipose Genes Under Epigenetic Regulation: Revealing New Mechanisms of Obesity Occurrence

by Weijing Wen, Simeng Gu, Fanjia Guo, Zhijian Chen, Sujun Yan and Zhe Mo

Curr. Issues Mol. Biol. 2025, 47(7), 540; https://doi.org/10.3390/cimb47070540 - 11 Jul 2025

Abstract

Obesity is a chronic metabolic disorder and a growing global public health challenge, affecting hundreds of millions of individuals worldwide. While diet and physical activity are well-established contributors, increasing evidence underscores the critical role of epigenetic mechanisms in mediating obesity-related processes. Epigenetic modifications—such [...] Read more.

Obesity is a chronic metabolic disorder and a growing global public health challenge, affecting hundreds of millions of individuals worldwide. While diet and physical activity are well-established contributors, increasing evidence underscores the critical role of epigenetic mechanisms in mediating obesity-related processes. Epigenetic modifications—such as DNA methylation, RNA methylation (particularly N6-methyladenosine), histone modifications, non-coding RNAs, and chromatin remodeling—modulate gene expression without altering the DNA sequence. This review aims to provide an overview of the epigenetic mechanisms involved in obesity, with an emphasis on their molecular functions and regulatory networks. Integrating findings from relevant studies, we discuss how these modifications influence obesity-related outcomes through regulating key processes such as adipocyte differentiation and energy metabolism. Advancing our understanding of epigenetic regulation may pave the way for novel, targeted strategies in the prevention and treatment of obesity. Full article

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

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16 pages, 1093 KiB

Open AccessArticle

Topical Application of Bio-Pulsed Avian MSC-Derived Extracellular Vesicles Enhances Hair Regrowth and Skin Rejuvenation: Evidence from Clinical Evaluation and miRNA Profiling

by Ju-Sheng Shieh, Yu-Tang Chin, Tsu-Te Yeh, Jiong Jiong Guo, Fung-Wei Chang, Hui-Rong Cheng, Hung-Han Hsu, Wei-Lun Huang, Han-Hsiang Huang, Ya-Yu Hsieh, Chien-Ping Chiang and Shih-Ching Wang

Curr. Issues Mol. Biol. 2025, 47(7), 539; https://doi.org/10.3390/cimb47070539 - 11 Jul 2025

Abstract

Small extracellular vesicles (sEVs) derived from mesenchymal stem cells have emerged as promising therapeutic agents in regenerative dermatology. This study evaluated the safety and efficacy of Bio-Pulsed avian mesenchymal stem cell-derived sEVs (AMSC-sEVs), topically applied for hair follicle stimulation and skin rejuvenation. Two [...] Read more.

Small extracellular vesicles (sEVs) derived from mesenchymal stem cells have emerged as promising therapeutic agents in regenerative dermatology. This study evaluated the safety and efficacy of Bio-Pulsed avian mesenchymal stem cell-derived sEVs (AMSC-sEVs), topically applied for hair follicle stimulation and skin rejuvenation. Two prospective, single-arm clinical trials were conducted: one involving 30 participants using a hair ampoule over 60 days, and the other involving 30 participants applying a facial essence for 28 days. Objective measurements demonstrated significant improvements in the anagen/telogen hair ratio, reduced shedding, increased collagen density, and reduced wrinkle depth and pigmentation. Small RNA sequencing and qPCR profiling confirmed that Bio-Pulsed AMSC-sEVs were enriched with regenerative microRNAs, such as miR-21-5p and miR-199a-5p, associated with anti-inflammatory and anti-aging effects. No adverse events were reported. These findings suggest that Bio-Pulsed AMSC-sEVs may offer a safe, non-invasive, and cell-free approach to enhance skin and hair regeneration in human subjects. Full article

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

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20 pages, 1826 KiB

Open AccessArticle

Antioxidant Activity of Radix Cyathula officinalis Kuan Polysaccharides and Their Modulatory Effects on the Gut Microbiota of Caenorhabditis elegans

by Rui Li, Xinyue Chen, Lijuan Wu, Lei Xie, Mengqiu Chen, Yujie Qiu, Fan Liu, Ji Chen and Mengliang Tian

Curr. Issues Mol. Biol. 2025, 47(7), 538; https://doi.org/10.3390/cimb47070538 - 11 Jul 2025

Abstract

Polysaccharides isolated from Radix Cyathula officinalis Kuan (RCP) are key bioactive components with immunomodulatory, antioxidant, and anti-inflammatory effects. Their efficacy varies according to their geographic origin and processing methods. However, the systemic anti-aging mechanisms and antioxidant efficacy of RCP have not yet been [...] Read more.

Polysaccharides isolated from Radix Cyathula officinalis Kuan (RCP) are key bioactive components with immunomodulatory, antioxidant, and anti-inflammatory effects. Their efficacy varies according to their geographic origin and processing methods. However, the systemic anti-aging mechanisms and antioxidant efficacy of RCP have not yet been comprehensively characterized. This study investigated the antioxidant and anti-aging effects of RCP in vitro and in vivo using a Caenorhabditis elegans heat stress model, comparing rRCP (RCP from raw samples) and wRCP (RCP from wine-processed samples) from key production areas. Among these, the RCP collected from the Zhonggang region exhibited the strongest antioxidant activity. Both rRCP and wRCP enhanced worms’ oxidative stress resistance, reduced their ROS levels, increased their antioxidant enzyme activities, prolonged their lifespan, and improved their reproductive capacity under thermal stress. Notably, the wRCP exhibited more pronounced benefits. Additionally, 16S rRNA sequencing revealed that RCP altered the gut microbiota’s composition by increasing its microbial diversity, enriching beneficial bacteria like Bacillus, and decreasing potential pathogens such as Escherichia and Citricoccus. The treatment also led to an increased abundance of Firmicutes and a slight reduction in Bacteroidetes. Collectively, these findings suggest that RCP, particularly wRCP, holds promise as a therapeutic agent for combating oxidative stress and promoting longevity, in part by modulating the gut microbiome. Full article

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

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11 pages, 766 KiB

Open AccessArticle

Serum Levels of IL-21 and IL-22 in Breast Cancer Patients—A Preliminary Study

by Jacek Kabut, Aleksandra Mielczarek-Palacz, Joanna Magdalena Gola, Elżbieta Chełmecka, Anita Gorzelak-Magiera, Patrycja Królewska-Daszczyńska, Sebastian Stępień, Jakub Szymon Wnuk and Iwona Gisterek-Grocholska

Curr. Issues Mol. Biol. 2025, 47(7), 537; https://doi.org/10.3390/cimb47070537 - 10 Jul 2025

Abstract

Breast cancer is one of the most commonly diagnosed malignant tumours in women worldwide. Although modern medicine has led to advanced diagnostic methods and therapies that allow for increasingly effective treatment, the mechanisms underlying breast cancer development and progression remain the subject of [...] Read more.

Breast cancer is one of the most commonly diagnosed malignant tumours in women worldwide. Although modern medicine has led to advanced diagnostic methods and therapies that allow for increasingly effective treatment, the mechanisms underlying breast cancer development and progression remain the subject of intensive research. In the pathogenesis of this cancer, significant importance is attributed to interactions between tumour cells and the tumour microenvironment, in which soluble immune system mediators—cytokines—play a key role, including IL-21 and IL-22. These interleukins, by modulating the immune response, can both promote and inhibit tumour progression, and analysing their concentrations may prove helpful in diagnosis, disease progression prognosis, and the development of new therapies, including immunotherapy. The aim of this study was to determine the concentrations of IL-21 and IL-22 in a group of patients with invasive cancer, depending on the biological type of the tumour and its malignancy grade. The study involved 60 women with breast cancer and 20 women with benign breast lesions, and the analysis of IL-21 and IL-22 protein concentrations was performed using the enzyme-linked immunosorbent assay (ELISA) method. The analysis shows that the concentrations of IL-21 and IL-22 do not differ significantly depending on the malignancy grade of the tumour. However, a statistically significant negative correlation between the concentrations of IL-21 and IL-22 was observed exclusively in the group of patients with benign breast lesions. Due to the high heterogeneity of breast cancers, further research with a larger study group is necessary to better understand these parameters and possibly apply them clinically in patients with breast cancer. Full article

(This article belongs to the Special Issue Early Molecular Diagnosis and Comprehensive Treatment of Tumors)

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17 pages, 2081 KiB

Open AccessArticle

Transcriptomic Analysis Reveals Candidate Hub Genes and Putative Pathways in Arabidopsis thaliana Roots Responding to Verticillium longisporum Infection

by Qiwei Zheng, Yangpujia Zhou and Sui Ni

Curr. Issues Mol. Biol. 2025, 47(7), 536; https://doi.org/10.3390/cimb47070536 - 10 Jul 2025

Abstract

Verticillium longisporum, a soil-borne fungus responsible for Verticillium wilt, primarily colonizes members of the Brassicaceae family. Using Arabidopsis thaliana roots as an experimental host, we systematically identify V. longisporum-responsive genes and pathways through comprehensive transcriptomic analysis, alongside screening of potential hub [...] Read more.

Verticillium longisporum, a soil-borne fungus responsible for Verticillium wilt, primarily colonizes members of the Brassicaceae family. Using Arabidopsis thaliana roots as an experimental host, we systematically identify V. longisporum-responsive genes and pathways through comprehensive transcriptomic analysis, alongside screening of potential hub genes and evaluation of infection-associated regulatory mechanisms. The GSE62537 dataset was retrieved from the Gene Expression Omnibus database. After performing GEO2R analysis and filtering out low-quality data, 222 differentially expressed genes (DEGs) were identified, of which 184 were upregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on these DEGs. A protein–protein interaction network was constructed using the STRING database. CytoHubba and CytoNCA plugins in Cytoscape v3.10.3 were used to analyze and evaluate this network; six hub genes and four functional gene modules were identified. The GeneMANIA database was used to construct a co-expression network for hub genes. Systematic screening of transcription factors within the 14 DEGs revealed the inclusion of the hub gene NAC042. Integrative bioinformatics analysis centered on NAC042 enabled prediction of a pathogen-responsive regulatory network architecture. We report V. longisporum-responsive components in Arabidopsis, providing insights for disease resistance studies in Brassicaceae crops. Full article

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

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13 pages, 1893 KiB

Open AccessArticle

The Effects of Engeletin on Insulin Resistance Induced in Human HepG2 Liver Cells

by Erdem Toktay, Secil Nazife Parlak, Tugba Kavas, Harun Un, Rustem Anıl Ugan and Muhammed Yayla

Curr. Issues Mol. Biol. 2025, 47(7), 535; https://doi.org/10.3390/cimb47070535 - 10 Jul 2025

Abstract

In this study, we aimed to investigate the effect of Engeletin (ENG) on insulin resistance and the associated oxidative cell damage in human HepG2 liver cells. The cells were grown in a cell culture medium, and insulin resistance was induced. After the determination [...] Read more.

In this study, we aimed to investigate the effect of Engeletin (ENG) on insulin resistance and the associated oxidative cell damage in human HepG2 liver cells. The cells were grown in a cell culture medium, and insulin resistance was induced. After the determination of the toxic and effective doses of Engeletin, the effects of Engeletin on insulin resistance and insulin resistance-induced oxidative damage, inflammation, and apoptosis. To induce IR, culture plates were treated with 30 mM glucose and 50 nM insulin and incubated for 48 h. Engeletin and metformin were given one hour before starting the insulin resistance induction. In the HepG2 cells, insulin resistance decreased glucose consumption, the expression of ISR-1 and ISR-2, and the GLUT-2 levels, while they were all increased by Engeletin, which showed a metformin-like effect. In addition, Engeletin alleviated oxidative cell damage by decreasing MDA levels, which increased due to insulin resistance-induced oxidative stress, increasing the GSH and SOD levels and decreasing the caspase-3 (Cas-3), caspase-9 (Cas-9), and tumor necrosis factor alpha (TNF-α) levels, which also increase under insulin resistance conditions. Engeletin was found to have the protective and therapeutic effect of reducing insulin resistance (IR) and the oxidative cell damage it causes in human HepG2 cells. Full article

(This article belongs to the Special Issue Natural Products as Potential Sources of Antidiabetic Compounds, 2nd Edition)

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21 pages, 1433 KiB

Open AccessReview

Itaconic Acid: A Regulator of Immune Responses and Inflammatory Metabolism

by Kai Ma, Pei Zhou, Wei Zhang, Liwu Zeng, Kaixiong Tao and Peng Zhang

Curr. Issues Mol. Biol. 2025, 47(7), 534; https://doi.org/10.3390/cimb47070534 - 9 Jul 2025

Abstract

This article reviews the multifaceted roles of itaconate in immune regulation and inflammatory metabolism. Itaconic acid is a dicarboxylic acid with anti-inflammatory, antioxidant, and anti-tumor properties. It is initially produced by the heating decomposition of citric acid and is closely related to the [...] Read more.

This article reviews the multifaceted roles of itaconate in immune regulation and inflammatory metabolism. Itaconic acid is a dicarboxylic acid with anti-inflammatory, antioxidant, and anti-tumor properties. It is initially produced by the heating decomposition of citric acid and is closely related to the tricarboxylic acid cycle. In immune regulation, itaconate regulates macrophage function through a variety of mechanisms, including metabolic reprogramming, polarization regulation, inhibition of cytokine production, and regulation of oxidative stress. It can also affect the function of T cells and B cells. In terms of inflammatory metabolism, itaconate can regulate the production of inflammatory factors, inhibit the activity of succinate dehydrogenase, and affect cellular energy metabolism and lipid metabolism. Its mechanism of action involves the inhibition of succinate dehydrogenase, covalent modification of proteins, influence on epigenetic modification, and playing a role through the G protein-coupled receptor OXGR1 (Oxoglutarate Receptor 1). Itaconic acid derivatives have shown good effects in anti-inflammation and anti-oxidation and have broad application prospects in clinical treatment, including the treatment of inflammatory diseases, anti-tumor and anti-microbial infection. However, the long-term safety and side effects of itaconic acid as a therapeutic agent still need to be further studied. Future studies will further explore the synthesis and function of itaconic acid in different cell types, its physiological effects in non-inflammatory conditions, and its potential application in clinical treatment in order to develop new therapeutic strategies and improve the treatment effect of chronic inflammatory and metabolism-related diseases. Full article

(This article belongs to the Special Issue Molecular Insights: Mechanisms Underlying the Biological Activities of Natural Products)

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15 pages, 1267 KiB

Open AccessReview

Plant Heteropolysaccharides as Potential Anti-Diabetic Agents: A Review

by Dan He and Can Cui

Curr. Issues Mol. Biol. 2025, 47(7), 533; https://doi.org/10.3390/cimb47070533 - 9 Jul 2025

Abstract

Diabetes mellitus (DM), a chronic metabolic disease, poses a significant challenge to global health. Although type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM), and other types of diabetes mellitus differ in pathological mechanisms, they converge in that [...] Read more.

Diabetes mellitus (DM), a chronic metabolic disease, poses a significant challenge to global health. Although type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM), and other types of diabetes mellitus differ in pathological mechanisms, they converge in that hyperglycemia is a universal clinical hallmark. Currently, the antidiabetic medications employed in clinical practice for blood glucose management require long-term administration and are associated with various side effects that can adversely impact human health. Plant heteropolysaccharides have emerged as promising candidates for anti-diabetic therapy, owing to their abundant natural sources, absence of toxicities, and confirmed hypoglycemic activities. This review aims to summarize the anti-diabetic mechanisms of plant heteropolysaccharides by dissecting the key biological pathways associated with clinical intervention in DM, including the modulation of insulin secretion, a reduction in insulin resistance, and an alteration in the composition of the gut microbiota. For these reasons, these findings provide a theoretical framework for the clinical application of plant heteropolysaccharides and indicate that they are expected to become natural agents used in treating DM. Full article

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

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15 pages, 1266 KiB

Open AccessArticle

Detection of the ST111 Global High-Risk Pseudomonas aeruginosa Clone in a Subway Underpass

by Balázs Libisch, Chioma Lilian Ozoaduche, Tibor Keresztény, Anniek Bus, Tommy Van Limbergen, Katalin Posta and Ferenc Olasz

Curr. Issues Mol. Biol. 2025, 47(7), 532; https://doi.org/10.3390/cimb47070532 - 9 Jul 2025

Abstract

P. aeruginosa strain NL201 was cultured from an urban water drain in a populated subway underpass as an environmental isolate for the ST111 global high-risk P. aeruginosa clone. In addition to carrying generally present intrinsic P. aeruginosa antibiotic resistance genes, this serotype O4 [...] Read more.

P. aeruginosa strain NL201 was cultured from an urban water drain in a populated subway underpass as an environmental isolate for the ST111 global high-risk P. aeruginosa clone. In addition to carrying generally present intrinsic P. aeruginosa antibiotic resistance genes, this serotype O4 isolate also carries a set of additional acquired resistance determinants, including aadA2, bla_OXA-10, sul1, and an aac(6′)-Ib family gene. The NL201 isolate features the bla_PDC-3 allele, which was found to confer significantly higher catalytic efficiency against cefepime and imipenem compared to bla_PDC-1, as well as the potent P. aeruginosa virulence factors exoS, exoT, and algD. Serotype O4 isolates of the ST111 global high-risk P. aeruginosa clone have been reported from clinical samples in Canada and the USA, human stool samples in France, and environmental samples (such as cosmetic, hospital drains, and urban water drain) from various European countries. These observations underscore the effective dissemination of the ST111 global high-risk P. aeruginosa clone between different hosts, environments, and habitats, and they warrant targeted investigations from a One Health perspective on the possible routes of its spread and molecular evolution. Full article

(This article belongs to the Special Issue Bioinformatics Research in Bacterial Genomics, Metagenomics and Metatranscriptomics: 2nd Edition)

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15 pages, 2509 KiB

Open AccessArticle

A New Tool to Decrease Interobserver Variability in Biomarker Annotation in Solid Tumor Tissue for Spatial Transcriptomic Analysis

by Sravya Palavalasa, Emily Baker, Jack Freeman, Aditri Gokul, Weihua Zhou, Dafydd Thomas, Wajd N. Al-Holou, Meredith A. Morgan, Theodore S. Lawrence and Daniel R. Wahl

Curr. Issues Mol. Biol. 2025, 47(7), 531; https://doi.org/10.3390/cimb47070531 - 9 Jul 2025

Abstract

Integrating spatial transcriptomic data with immunofluorescence image data is challenging using existing tools due to their differences in spatial resolution. Immunofluorescence provides information about protein expression at the cellular or subcellular level, whereas spatial transcriptomic platforms typically rely on multicellular “spots” for RNA [...] Read more.

Integrating spatial transcriptomic data with immunofluorescence image data is challenging using existing tools due to their differences in spatial resolution. Immunofluorescence provides information about protein expression at the cellular or subcellular level, whereas spatial transcriptomic platforms typically rely on multicellular “spots” for RNA profiling. Our study coupled spatial transcriptomics of irradiated glioblastoma tissues with immunofluorescence for γH2AX, a marker of DNA damage within the nuclei of cells. We then compared gene expression in γH2AX-positive and negative regions within the tissue. There was significant interobserver variability in manual annotation of γH2AX positivity in multicellular spots by three different researchers (Kappa statistic = 0.345), despite all of them being familiar with γH2AX immunofluorescence and having predefined imaging parameters for annotation. This variability led to different researchers nominating different genes as being associated with DNA repair. To overcome this problem, we have developed a new tool using MATLAB. This tool performs “spot”-wise image analysis and uses researcher-defined parameters such as immunofluorescent marker intensity threshold and number of positive cells to annotate the “spots” as γH2AX positive or negative. The tissue with the most variability in manual annotation was annotated reproducibly by our MATLAB tool, leading to reproducible downstream analysis. Full article

(This article belongs to the Topic Single-Cell Technologies: From Research to Application)

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11 pages, 253 KiB

Open AccessArticle

Association of Nrf2 Single Nucleotide Polymorphism rs35652124 and FABP4 Levels with Peripheral Artery Disease Among Type 2 Diabetes Mellitus Pakistani Population

by Iqra Ayaz, Nakhshab Choudhry, Amna Ihsan, Tehreem Zubair, Aamir Jamal Gondal and Nighat Yasmin

Curr. Issues Mol. Biol. 2025, 47(7), 530; https://doi.org/10.3390/cimb47070530 - 9 Jul 2025

Abstract

Peripheral arterial disease (PAD) is a macrovascular diabetic complication, characterized by atherosclerotic plaque formation due to hyperglycemia and dyslipidemia. The molecular mechanisms involved in PAD-T2DM pathogenesis will help in understanding and early prognosis; therefore, we aim to evaluate FABP4 levels and Nrf2 single-nucleotide [...] Read more.

Peripheral arterial disease (PAD) is a macrovascular diabetic complication, characterized by atherosclerotic plaque formation due to hyperglycemia and dyslipidemia. The molecular mechanisms involved in PAD-T2DM pathogenesis will help in understanding and early prognosis; therefore, we aim to evaluate FABP4 levels and Nrf2 single-nucleotide polymorphisms (SNPs) among PAD-T2DM patients. In a case-control study, 123 samples (healthy control HC, T2DM, and PAD-T2DM; n = 41 each) were collected from the diabetic foot clinic at Mayo Hospital, Lahore. Baseline and biochemical data were collected. PAD diagnosis was established by measuring the ankle-brachial index with color Doppler ultrasound. Serum FABP4 levels were measured using an ELISA. Nrf2 SNP rs35652124 analysis was performed by restriction fragment length polymorphism. PAD-T2DM prevalence was higher among male subjects (61.1%). Fasting plasma glucose levels (p = 0.02), total cholesterol (p < 0.0001), and LDL-cholesterol (p = 0.01) were significantly higher in PAD-T2DM as compared to T2DM. SNP association analysis showed that homozygous genotype TT (OR: 3.85, 95% (CI): 1.22–12.11, p = 0.02) and T-allele (OR: 1.31, 95% (CI): 1.31–4.67, p = 0.005) were significantly associated with PAD-T2DM. FABP4 levels were higher in the PAD-T2DM group as compared to T2DM (p < 0.0001) and were significantly associated with Nrf2 SNP genotype TT (p < 0.001) and CT (p = 0.01) in PAD-T2DM. Our results showed, for the first time, that the Nrf2 SNP is significantly associated with PAD-T2DM and FABP4 levels compared to T2DM. Full article

(This article belongs to the Special Issue Insights from Genetics, Epigenetics, and Microbiome Research in Obesity: Integrative Approaches to Understand Metabolic Disorders)

16 pages, 1165 KiB

Open AccessArticle

Sensitisation of HeLa Cell Cultures to Xanthone Treatment by RNAi-Mediated Silencing of NANOG and STAT3

by Oliwia Gruszka, Dorota Żelaszczyk, Henryk Marona and Ilona Anna Bednarek

Curr. Issues Mol. Biol. 2025, 47(7), 529; https://doi.org/10.3390/cimb47070529 - 9 Jul 2025

Abstract

The increasing morbidity of various types of cancer in the world’s population and the limited number of universal methods of their treatment contribute to the growth in research into the development of new treatment strategies. Most of this research focuses on treatments that [...] Read more.

The increasing morbidity of various types of cancer in the world’s population and the limited number of universal methods of their treatment contribute to the growth in research into the development of new treatment strategies. Most of this research focuses on treatments that target specific factors in cancer cell signalling pathways. There is also great interest in drugs derived from natural substances, as these represent one of the largest sources of potential pharmaceuticals. In our analysis, we focused on the action of α-mangostin and gambogic acid, which are natural xanthones or their synthetic derivatives. We studied their influence on the expression of STAT3 and NANOG, which play a confirmed role in different stages of cancer development. For this purpose, we applied RNAi-mediated gene silencing of NANOG and STAT3 to enhance the efficacy of xanthone-based anticancer treatment in HeLa cell cultures. After stimulating the cells with xanthones, we determined the expression of the tested transcription factors and the ROS level. In addition, we determined the cytotoxicity and apoptosis of the cells. Our research results confirm the anticancer efficacy of the analysed xanthones and demonstrate the role of the tested transcription factors. Silencing these factors makes cancer cells more susceptible to xanthone treatment. Full article

(This article belongs to the Section Molecular Pharmacology)

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17 pages, 7749 KiB

Open AccessArticle

Dihydroartemisinin Alleviates the Symptoms of a Mouse Model of Systemic Lupus Erythematosus Through Regulating Splenic T/B-Cell Heterogeneity

by Haihong Qin, Xiaohua Zhu, Xiao Liu, Yilun Wang, Jun Liang, Hao Wu and Jinfeng Wu

Curr. Issues Mol. Biol. 2025, 47(7), 528; https://doi.org/10.3390/cimb47070528 - 9 Jul 2025

Abstract

Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with significant therapeutic challenges. Recent studies suggest that dihydroartemisinin (DHA), a traditional Chinese medicine known for its anti-malarial properties, may be beneficial for SLE treatment, although its precise mechanism remains unclear. This [...] Read more.

Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with significant therapeutic challenges. Recent studies suggest that dihydroartemisinin (DHA), a traditional Chinese medicine known for its anti-malarial properties, may be beneficial for SLE treatment, although its precise mechanism remains unclear. This study aimed to investigate the effects of DHA on the cellular composition and molecular events of splenic T cells and B cells in MRL/lpr mice, a widely used SLE model. Methods: T cells and B cells isolated from the spleens of three DHA-treated mice and three control mice underwent single-cell RNA sequencing (scRNA-seq) using the 10× Genomics Chromium system. Comprehensive analyses included cell clustering, signaling pathway enrichment, pseudotime trajectory analysis, and cellular communication assessment using unbiased computational methods. Results: DHA treatment significantly reduced kidney inflammation and altered the proportions of splenic T cells and B cells, particularly decreasing plasma cells. Molecular profiling of effector CD4+ T cells showed a significant reduction in several inflammation-related signaling pathways in DHA-treated mice. Cellular communication analysis indicated altered interactions between effector CD4+ T cells and B cells in MRL/lpr mice after DHA treatment. Conclusions: Our findings reveal changes in cellular composition and signaling pathways in splenic T cells and B cells of MRL/lpr mice following DHA treatment. DHA may inhibit B-cell differentiation into plasma cells by modulating effector CD4+ T cells, potentially through the regulation of HIF1α and ligand–receptor interactions, enhancing our understanding of DHA’s mechanisms in SLE treatment. Full article

(This article belongs to the Special Issue Molecular Biology in Drug Design and Precision Therapy)

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13 pages, 674 KiB

Open AccessReview

Phytochemicals in Breast Cancer Prevention and Therapy: Mechanisms, Efficacy, and Future Prospects

by Neha Kodali, Chikezie O. Madu and Yi Lu

Curr. Issues Mol. Biol. 2025, 47(7), 527; https://doi.org/10.3390/cimb47070527 - 8 Jul 2025

Abstract

Breast cancer is one of the most common forms of cancer in women globally. Phytochemicals are naturally occurring compounds in plants that have been the focus of many research studies for their potential in cancer prevention and treatment. This review will explore the [...] Read more.

Breast cancer is one of the most common forms of cancer in women globally. Phytochemicals are naturally occurring compounds in plants that have been the focus of many research studies for their potential in cancer prevention and treatment. This review will explore the mechanisms certain phytochemicals use to interact with the cellular pathways involved in breast cancer development. Phytochemicals modulate various processes such as apoptosis, cell cycle regulation, angiogenesis, and metastasis to potentially combat breast cancer. This review will also examine different dietary sources of phytochemicals, the potential for integration of phytochemicals into breast cancer therapy, the safety, toxicity, and limitations of phytochemicals, and the future of phytochemicals in the context of breast cancer. Full article

(This article belongs to the Special Issue Phytochemicals in Cancer Chemoprevention and Treatment: 2nd Edition)

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