Current Issues in Molecular Biology

15 pages, 5066 KiB

Open AccessArticle

Mitochondrial Genomes of Four Millipedes (Diplopoda: Spirostreptida and Spirobolida) Unveil Phylogenetic Novelty and Gene Rearrangement Patterns

by Yingzhu Li, Gaoji Zhang, Wei Xu, Tangjun Xu, Lingna Li, Ming Gao, Jiachen Wang and Hongyi Liu

Curr. Issues Mol. Biol. 2025, 47(6), 476; https://doi.org/10.3390/cimb47060476 - 19 Jun 2025

Viewed by 330

Abstract

Millipedes (Diplopoda) are crucial decomposers in soil ecosystems, as they play a vital role in organic matter degradation while also holding potential as bioindicators of environmental health. This study deciphered the complete mitogenomes of four millipede species (Diplopoda: Spirostreptida and Spirobolida) using next-generation [...] Read more.

Millipedes (Diplopoda) are crucial decomposers in soil ecosystems, as they play a vital role in organic matter degradation while also holding potential as bioindicators of environmental health. This study deciphered the complete mitogenomes of four millipede species (Diplopoda: Spirostreptida and Spirobolida) using next-generation sequencing technology, thus revealing evolutionary relationships among diplopod taxa and characterizing mitochondrial genomic features. The full mitochondrial sequences of Agaricogonopus acrotrifoliolatus, Bilingulus sinicus, Paraspirobolus lucifugus, and Trigoniulus corallinus, ranged in size from 14,906 to 15,879 bp, with each containing 37 typical genes and one D-loop region. Notably, the D-loop regions of A. acrotrifoliolatus and B. sinicus were positioned atypically, thus indicating structural rearrangements. A nucleotide composition analysis revealed pronounced AT-skews, with tRNA sequences exhibiting the highest A+T content. Ka/Ks ratios demonstrated that the ND5 gene experienced the weakest purifying selection pressure, thus suggesting its potential role in adaptive evolution. The results of the phylogenetic analysis showed genetic relationships between the three orders of ((Julida, Spirostreptida), Spirobolida), which was inconsistent with the previous conclusion regarding the three orders, obtained through morphological studies: ((Julida, Spirobolida), Spirostreptida). These findings highlight the role of the mitochondrial genome in resolving phylogenetic conflicts and provide important insights for further studies on millipedes. Full article

(This article belongs to the Special Issue Mitochondrial Genomes 2025: Unraveling the Threads of Evolution and Function)

► Show Figures

Figure 1

47 pages, 986 KiB

Open AccessReview

Integrating Genomics and Molecular Biology in Understanding Peritoneal Adhesion

by Mirela Lungu, Claudiu N. Lungu, Andreea Creteanu and Mihaela C. Mehedinti

Curr. Issues Mol. Biol. 2025, 47(6), 475; https://doi.org/10.3390/cimb47060475 - 19 Jun 2025

Viewed by 373

Abstract

Peritoneal adhesions following surgical injury remain a major clinical challenge, often resulting in severe complications, such as intestinal obstruction, chronic pain, and infertility. This review systematically integrates recent genomic and molecular biology insights into the pathogenesis of peritoneal adhesions, explicitly focusing on molecular [...] Read more.

Peritoneal adhesions following surgical injury remain a major clinical challenge, often resulting in severe complications, such as intestinal obstruction, chronic pain, and infertility. This review systematically integrates recent genomic and molecular biology insights into the pathogenesis of peritoneal adhesions, explicitly focusing on molecular pathways, including TGF-β signaling, COX-2-mediated inflammatory responses, fibrinolytic balance (tPA/PAI-1), angiogenesis pathways (VEGF, PDGF), and extracellular matrix remodeling (MMPs/TIMPs). Newly conducted transcriptomic and proteomic analyses highlight distinct changes in gene expression patterns in peritoneal fibroblasts during adhesion formation, pinpointing critical roles for integrins, cadherins, selectins, and immunoglobulin superfamily molecules. Recent studies indicate significant shifts in TGF-β isoforms expression, emphasizing isoform-specific impacts on fibrosis and scarring. These insights reveal substantial knowledge gaps, particularly the differential regulatory mechanisms involved in fibrosis versus normal reparative reperitonealization. Future therapeutic strategies could target these molecular pathways and inflammatory mediators to prevent or reduce adhesion formation. Further research into precise genetic markers and the exploration of targeted pharmacological interventions remain pivotal next steps in mitigating postoperative adhesion formation and improving clinical outcomes. Full article

(This article belongs to the Special Issue Molecular Keys to Bioactivity: Pharmacophore and SAR Exploration in Organic Compounds)

► Show Figures

Figure 1

14 pages, 3426 KiB

Open AccessArticle

L-Ascorbic Acid (LAA) Supplementation as a Potential Treatment for Skin Aging: Regulation of Adipose Tissue Mesenchymal Stem Cells (AT-MSCs) Protein Secretion

by Komang Ardi Wahyuningsih, I. Gede Eka Wiratnaya, I. Wayan Weta, I. Gde Raka Widiana, Wimpie I. Pangkahila, Ida Ayu Ika Wahyuniari, I. Made Muliarta, Veronika Maria Sidharta and Assyafiya Salwa

Curr. Issues Mol. Biol. 2025, 47(6), 474; https://doi.org/10.3390/cimb47060474 - 19 Jun 2025

Viewed by 360

Abstract

Skin aging is mostly caused by the accumulation of reactive oxygen species (ROS) that lead to cellular dysfunction. One promising therapy for skin aging is the secretome product of adipose tissue mesenchymal stem cells (AT-MSCs). L-ascorbic acid (LAA) is an essential molecule for [...] Read more.

Skin aging is mostly caused by the accumulation of reactive oxygen species (ROS) that lead to cellular dysfunction. One promising therapy for skin aging is the secretome product of adipose tissue mesenchymal stem cells (AT-MSCs). L-ascorbic acid (LAA) is an essential molecule for preventing oxidative stress as an external antioxidant agent and has been used in chemical therapy for skin aging. In this study, we evaluated the effects of LAA on cell morphology, the number of cells, cell viability, and the paracrine secretion of preconditioned AT-MSCs in in vitro culture with LAA in 100 and 200 µg/mL compared with an untreated culture with LAA as a control. LAA supplementation in both concentrations improved the morphology of cells without affecting the cell viability. However, there was no significant improvement in the number of cells even though the trend showed an enhancement of the number of cells. The total protein of the secretome decreased in the LAA preconditioning group. However, preconditioning AT-MSCs in in vitro culture with LAA improved the levels of insulin-like growth factor 1 (IGF-1), transforming growth factor β1 (TGF-β1), and interleukin 6 (IL-6) which are essential proteins for skin aging in regulating ROS. Full article

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

► Show Figures

Graphical abstract

12 pages, 1531 KiB

Open AccessArticle

Association of DROSHA Variants with Susceptibility and Outcomes in Childhood Acute Lymphoblastic Leukemia

by Ioannis Kyriakidis, Iordanis Pelagiadis, Charalampos Pontikoglou, Helen A. Papadaki and Eftichia Stiakaki

Curr. Issues Mol. Biol. 2025, 47(6), 473; https://doi.org/10.3390/cimb47060473 - 19 Jun 2025

Viewed by 334

Abstract

MicroRNAs are key regulators of lymphoid differentiation, exhibiting a pivotal role in acute lymphoblastic leukemia (ALL) biology and prognosis. The initial steps of canonical miRNA biogenesis involve the microprocessor complex processing the primary miRNA transcripts into precursor miRNAs via Drosha. DROSHA polymorphisms have [...] Read more.

MicroRNAs are key regulators of lymphoid differentiation, exhibiting a pivotal role in acute lymphoblastic leukemia (ALL) biology and prognosis. The initial steps of canonical miRNA biogenesis involve the microprocessor complex processing the primary miRNA transcripts into precursor miRNAs via Drosha. DROSHA polymorphisms have been implicated in pediatric ALL and linked with cancer risk. This study investigated the role of rs642321, rs3805500, and rs10035440 DROSHA polymorphisms in ALL susceptibility, relapse, and outcomes in children and adolescents of Greek descent. The study included 252 children and adolescents (115 ALL cases and 137 controls). Genotyping was performed using RT-qPCR and the TaqMan Genotyping Assay. Homozygotes for the minor allele in DROSHA rs642321 were nominally associated with ALL susceptibility (TT vs. CC+CT; OR 4.5; 95% CI: 1.2–21.2; p_adj = 0.034). Likewise, homozygotes for the minor allele in rs3805500 were linked with ALL risk (GG vs. AA+AG; OR 2.7; 95% CI: 1.3–6.1; p_adj = 0.012). A suggestive association was observed between the rs3805500 AG genotype and both relapsed (OR 5.8; 95% CI: 1.6–24.3; p_adj = 0.011) and deceased cases (OR 5; 95% CI: 1.1–26.3; p_adj = 0.038). Patients with the rs3805500 AG and GG genotypes showed a trend toward poorer overall survival rates. In summary, certain haplotypes of DROSHA polymorphisms may be modestly associated with the occurrence of childhood ALL and its outcomes, although these findings require validation in larger, independent cohorts. Full article

(This article belongs to the Special Issue Genomic Analysis of Common Disease, 2nd Edition)

► Show Figures

Figure 1

22 pages, 389 KiB

Open AccessReview

Copper Nanoparticles in Aquatic Environment: Release Routes and Oxidative Stress-Mediated Mechanisms of Toxicity to Fish in Various Life Stages and Future Risks

by Anna Sielska and Lidia Skuza

Curr. Issues Mol. Biol. 2025, 47(6), 472; https://doi.org/10.3390/cimb47060472 - 19 Jun 2025

Viewed by 388

Abstract

The final recipient of nanoparticles, including various types of copper-based nanoparticles (Cu-based NPs), is the aquatic environment. Their increased production, especially as a component of antimicrobial agents, raises concerns about uncontrolled environmental release and subsequent ecological risks. The high reactivity of Cu-based NPs [...] Read more.

The final recipient of nanoparticles, including various types of copper-based nanoparticles (Cu-based NPs), is the aquatic environment. Their increased production, especially as a component of antimicrobial agents, raises concerns about uncontrolled environmental release and subsequent ecological risks. The high reactivity of Cu-based NPs enables interactions with biotic and abiotic environmental components, leading to bioaccumulation and disorders in living organisms, such as fish in various life stages, especially in embryos or hatchlings. Increasing concentration of Cu-based NPs causes various toxic effects, mainly through the induction of oxidative stress. These effects include impairment of antioxidant mechanisms, as well as damage to genetic material, cells and tissues, growth retardation, metabolic disorders, increased mortality, or hatching inhibition. The aim of this review is to describe the release routes of Cu-based NPs and their adverse effects on fish, while emphasizing the need for further research on their toxicity and measures to control their release to the environment. Given the limited data on the toxicity of Cu-based NPs, especially concerning sensitive fish developmental stages, further studies are required. Full article

(This article belongs to the Special Issue Innovations in Marine Biotechnology and Molecular Biology)

19 pages, 3071 KiB

Open AccessReview

The Known Unknowns: An Enigmatic Pathway of C₁₇-Polyacetylenic Oxylipins in Carrot (Daucus carota L.)

by Abdul Wakeel Umar, Hamad Hussain and Naveed Ahmad

Curr. Issues Mol. Biol. 2025, 47(6), 471; https://doi.org/10.3390/cimb47060471 - 19 Jun 2025

Viewed by 362

Abstract

C₁₇-polyacetylenic (PA) oxylipins are bioactive compounds in carrots (Daucus carota L.) with structurally unique features and diverse biological roles. These PA-derived compounds have garnered attention for their potential contributions to human health, particularly in cancer prevention and anti-inflammatory applications. This [...] Read more.

C₁₇-polyacetylenic (PA) oxylipins are bioactive compounds in carrots (Daucus carota L.) with structurally unique features and diverse biological roles. These PA-derived compounds have garnered attention for their potential contributions to human health, particularly in cancer prevention and anti-inflammatory applications. This trade-off between health benefits and sensory quality underscores the importance of understanding the genetic and biochemical basis of PA biosynthesis, as it may allow for the development of carrots with optimized levels of these compounds that balance both nutritional and sensory qualities. In this review, we seek biochemically inspired strategies to elucidate the complexities of PA-derived oxylipins biosynthesis in carrots, a topic that remains largely unexplored. By integrating current knowledge on polyacetylene biology, biosynthesis, genetic and enzymatic factors involved in their production and the implications for enhancing the medicinal value of carrots we aim to provide a foundation for future research that could unlock the full potential of carrots as a source of health-promoting bioactive compounds. Full article

(This article belongs to the Special Issue Molecular Mechanism of Plant Growth, Development and Secondary Metabolism)

► Show Figures

Figure 1

26 pages, 916 KiB

Open AccessReview

Integrating Artificial Intelligence in Next-Generation Sequencing: Advances, Challenges, and Future Directions

by Konstantina Athanasopoulou, Vasiliki-Ioanna Michalopoulou, Andreas Scorilas and Panagiotis G. Adamopoulos

Curr. Issues Mol. Biol. 2025, 47(6), 470; https://doi.org/10.3390/cimb47060470 - 19 Jun 2025

Viewed by 735

Abstract

The integration of artificial intelligence (AI) into next-generation sequencing (NGS) has revolutionized genomics, offering unprecedented advancements in data analysis, accuracy, and scalability. This review explores the synergistic relationship between AI and NGS, highlighting its transformative impact across genomic research and clinical applications. AI-driven [...] Read more.

The integration of artificial intelligence (AI) into next-generation sequencing (NGS) has revolutionized genomics, offering unprecedented advancements in data analysis, accuracy, and scalability. This review explores the synergistic relationship between AI and NGS, highlighting its transformative impact across genomic research and clinical applications. AI-driven tools, including machine learning and deep learning, enhance every aspect of NGS workflows—from experimental design and wet-lab automation to bioinformatics analysis of the generated raw data. Key applications of AI integration in NGS include variant calling, epigenomic profiling, transcriptomics, and single-cell sequencing, where AI models such as CNNs, RNNs, and hybrid architectures outperform traditional methods. In cancer research, AI enables precise tumor subtyping, biomarker discovery, and personalized therapy prediction, while in drug discovery, it accelerates target identification and repurposing. Despite these advancements, challenges persist, including data heterogeneity, model interpretability, and ethical concerns. This review also discusses the emerging role of AI in third-generation sequencing (TGS), addressing long-read-specific challenges, like fast and accurate basecalling, as well as epigenetic modification detection. Future directions should focus on implementing federated learning to address data privacy, advancing interpretable AI to improve clinical trust and developing unified frameworks for seamless integration of multi-modal omics data. By fostering interdisciplinary collaboration, AI promises to unlock new frontiers in precision medicine, making genomic insights more actionable and scalable. Full article

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

► Show Figures

Graphical abstract

16 pages, 3913 KiB

Open AccessArticle

Isolation and Characterization of Enterococcus faecalis Phage ZXL-01 and Preliminary Investigation of Its Therapeutic Effect on Periapical Periodontitis

by Hailin Jiang, Xueli Zhao, Chuhan Wang, Hongyan Shi, Jinghua Li, Chunyan Zhao and Honglan Huang

Curr. Issues Mol. Biol. 2025, 47(6), 469; https://doi.org/10.3390/cimb47060469 - 18 Jun 2025

Viewed by 307

Abstract

Enterococcus faecalis (E. faecalis) is a major pathogen responsible for refractory apical periodontitis (RAP). It can penetrate deep into dentinal tubules, form persistent biofilms, and exhibit antibiotic resistance, thereby limiting the efficacy of conventional antimicrobial treatments. Bacteriophages (phages), due to their [...] Read more.

Enterococcus faecalis (E. faecalis) is a major pathogen responsible for refractory apical periodontitis (RAP). It can penetrate deep into dentinal tubules, form persistent biofilms, and exhibit antibiotic resistance, thereby limiting the efficacy of conventional antimicrobial treatments. Bacteriophages (phages), due to their strong lytic activity and host specificity, have emerged as promising alternatives. In this study, a novel strictly lytic phage, ZXL-01, was isolated from lake water in Jilin, China. ZXL-01 demonstrated remarkable stability under extreme conditions, including thermal tolerance at 60 °C for 1 h and a wide pH range (4–11). Whole-genome sequencing (GenBank accession number: ON113334) revealed a genome of 40,804 bp with no virulence or tRNA genes, confirming its identity as an E. faecalis phage. Importantly, ZXL-01 exhibited potent antibiofilm activity, reducing biofilm biomass by approximately 69.4% in the inhibition group and 68.4% in the lysis group (both p < 0.001). In an in vitro root canal infection model induced by E. faecalis, scanning electron microscope (SEM) observations confirmed that ZXL-01 effectively inhibited biofilm formation and disrupted mature biofilms. These findings highlight the potential of ZXL-01 as a novel antimicrobial agent for the treatment of E. faecalis-associated apical periodontitis. Full article

(This article belongs to the Section Molecular Microbiology)

► Show Figures

Figure 1

12 pages, 2008 KiB

Open AccessArticle

Restoration of Hair Luster via Novel Biomarker COL7A1 by Minoxidil, Caffeine, and Biotin

by Ngoc Ha Nguyen, Young In Lee, Hyeon-Ah Do, Inhee Jung, Jae Hyun Park, Sung Jun Lee and Ju Hee Lee

Curr. Issues Mol. Biol. 2025, 47(6), 468; https://doi.org/10.3390/cimb47060468 - 18 Jun 2025

Viewed by 459

Abstract

Hair luster, a key component of visual hair quality, depends largely on the integrity of the cuticle. While cosmetic products offer temporarily enhanced luster, their effects are limited due to a poor understanding of the underlying molecular mechanisms. In this study, we employed [...] Read more.

Hair luster, a key component of visual hair quality, depends largely on the integrity of the cuticle. While cosmetic products offer temporarily enhanced luster, their effects are limited due to a poor understanding of the underlying molecular mechanisms. In this study, we employed a UVB-induced mouse model of hair luster loss to identify differentially expressed genes via quantitative real-time reverse transcription PCR. Key candidate genes were subsequently validated in vitro using human hair follicle dermal papilla cells and in ex vivo human scalp hair follicle tissue models. Subsequently, we evaluated the effects of minoxidil, caffeine, and biotin on gene expression and luster restoration. UVB exposure suppressed several luster-related genes, with COL7A1 consistently downregulated across all models. Treatment with minoxidil, caffeine, and biotin restored the expression of COL7A1 along with KRTAP5-5, KRTAP5-4, TGM3, and PTK7. These findings highlight COL7A1 as a novel molecular marker for hair luster and support its modulation as a potential therapeutic strategy. Full article

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

► Show Figures

Graphical abstract

17 pages, 2428 KiB

Open AccessArticle

Design of New Primer Sets for the Development of a Loop-Mediated Isothermal Amplification for Rapid Detection of Neisseria meningitidis

by Cuong Viet Vo, Trang Thu Nguyen, Huong Thu Ngo, Lan Anh Thi Bui, Toan Van Trinh, Loan Thi Vu, Hieu Dang Hoang and Phong Quoc Truong

Curr. Issues Mol. Biol. 2025, 47(6), 467; https://doi.org/10.3390/cimb47060467 - 17 Jun 2025

Viewed by 377

Abstract

Neisseria meningitidis is a pathogenic bacterial agent that causes meningococcal meningitis in humans. Developing a rapid and low-cost N. meningitidis detection method is crucial, especially for developing countries. This study focuses on the development of an efficient loop-mediated isothermal amplification (LAMP) method for [...] Read more.

Neisseria meningitidis is a pathogenic bacterial agent that causes meningococcal meningitis in humans. Developing a rapid and low-cost N. meningitidis detection method is crucial, especially for developing countries. This study focuses on the development of an efficient loop-mediated isothermal amplification (LAMP) method for accurate N. meningitidis identification. A new LAMP primer set was designed, and a LAMP reaction was optimized. The colorimetric detection method was also applied, and the assay characteristics were evaluated using clinical samples. The results demonstrated a specific LAMP reaction for N. meningitidis detection of genotypes A, B, and C, with a limit of detection of 10² cfu/mL, 100% specificity and sensitivity, and a rapid detection time of only 40 min by colorimetric visual inspection. No cross-reactivity with reference strains of Streptococcus pneumoniae, Staphylococcus aureus, Neisseria lactamica, Mycobacterium tuberculosis, and Haemophilus influenzae type b was observed in the LAMP reaction with the new primer set. This result suggests that the LAMP reaction could be a promising tool for developing a rapid N. meningitidis detection method suitable for use in Vietnam and other developing countries. Full article

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

► Show Figures

Figure 1

21 pages, 16644 KiB

Open AccessArticle

Artificial Intelligence Approach in Machine Learning-Based Modeling and Networking of the Coronavirus Pathogenesis Pathway

by Shihori Tanabe, Sabina Quader, Ryuichi Ono, Hiroyoshi Y. Tanaka, Akihisa Yamamoto, Motohiro Kojima, Edward J. Perkins and Horacio Cabral

Curr. Issues Mol. Biol. 2025, 47(6), 466; https://doi.org/10.3390/cimb47060466 - 17 Jun 2025

Viewed by 391

Abstract

The coronavirus pathogenesis pathway, which consists of severe acute respiratory syndrome (SARS) coronavirus infection and signaling pathways, including the interferon pathway, the transforming growth factor beta pathway, the mitogen-activated protein kinase pathway, the apoptosis pathway, and the inflammation pathway, is activated upon coronaviral [...] Read more.

The coronavirus pathogenesis pathway, which consists of severe acute respiratory syndrome (SARS) coronavirus infection and signaling pathways, including the interferon pathway, the transforming growth factor beta pathway, the mitogen-activated protein kinase pathway, the apoptosis pathway, and the inflammation pathway, is activated upon coronaviral infection. An artificial intelligence approach based on machine learning was utilized to develop models with images of the coronavirus pathogenesis pathway to predict the activation states. Data on coronaviral infection held in a database were analyzed with Ingenuity Pathway Analysis (IPA), a network pathway analysis tool. Data related to SARS coronavirus 2 (SARS-CoV-2) were extracted from more than 100,000 analyses and datasets in the IPA database. A total of 27 analyses, including nine analyses of SARS-CoV-2-infected human-induced pluripotent stem cells (iPSCs) and iPSC-derived cardiomyocytes and fibroblasts, and a total of 22 analyses of SARS-CoV-2-infected lung adenocarcinoma (LUAD), were identified as being related to “human” and “SARS coronavirus 2” in the database. The coronavirus pathogenesis pathway was activated in SARS-CoV-2-infected iPSC-derived cells and LUAD cells. A prediction model was developed in Python 3.11 using images of the coronavirus pathogenesis pathway under different conditions. The prediction model of activation states of the coronavirus pathogenesis pathway may aid in treatment identification. Full article

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

► Show Figures

Figure 1

24 pages, 8367 KiB

Open AccessArticle

by Zuming Xiong, Yirong Lin, Yongjun Yang, Wenxin Li, Wei Huang and Sen Zhang

Curr. Issues Mol. Biol. 2025, 47(6), 465; https://doi.org/10.3390/cimb47060465 - 17 Jun 2025

Viewed by 330

Abstract

Expression patterns and underlying mechanisms of metabolism-related genes SMOX and SUCLG2 in pan-cancer remain unclear. We conducted a comprehensive pan-cancer analysis of SMOX and SUCLG2, to explore their potential roles and mechanisms of action. Comprehensive analysis of SMOX and SUCLG2 was performed through [...] Read more.

Expression patterns and underlying mechanisms of metabolism-related genes SMOX and SUCLG2 in pan-cancer remain unclear. We conducted a comprehensive pan-cancer analysis of SMOX and SUCLG2, to explore their potential roles and mechanisms of action. Comprehensive analysis of SMOX and SUCLG2 was performed through UCSC, TCGA, GEO, and other databases. We validated the expression levels, diagnostic value, and prognostic significance of SMOX and SUCLG2 in CRC using external databases and qPCR. Then, CCK-8 is used to detect proliferation of RKO and HCT116 after silencing or overexpressing of SUCLG2. The expression of SMOX was upregulated and that of SUCLG2 was downregulated in most cancers. Both SMOX and SUCLG2 exhibited significant correlations with cancer prognosis, tumor microenvironment, immune infiltration, stemness scores, tumor mutational burden, and microsatellite instability. The diagnostic and prognostic value of SMOX and SUCLG2 in CRC was confirmed through TCGA, GEO, and HPA, as well as qPCR. SUCLG2 overexpression inhibited the proliferation of RKO and HCT116, whereas SUCLG2 silence promoted their proliferation. Our data provide insights into the role of SMOX and SUCLG2 in pan-cancer, highlighting their association with prognosis, cancer immunity, and other cancer characteristics and also revealing their significance in cancer progression. SUCLG2 may inhibit the proliferation of CRC. Full article

(This article belongs to the Collection Bioinformatics Approaches to Biomedicine)

► Show Figures

Figure 1

27 pages, 2280 KiB

Open AccessReview

Reactive Oxygen Species as Key Molecules in the Pathogenesis of Alcoholic Fatty Liver Disease and Nonalcoholic Fatty Liver Disease: Future Perspectives

by Zhiqing Zhang, Hong Yang, Fei Han and Peng Guo

Curr. Issues Mol. Biol. 2025, 47(6), 464; https://doi.org/10.3390/cimb47060464 - 17 Jun 2025

Cited by 1 | Viewed by 358

Abstract

Reactive oxygen species (ROS) are central to the progression of alcoholic fatty liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD). In ALD, ROS arise from alcohol metabolism (CYP2E1 and ADH/ALDH2), causing oxidative damage and fibrosis. In NAFLD, mitochondrial dysfunction, ER stress, and [...] Read more.

Reactive oxygen species (ROS) are central to the progression of alcoholic fatty liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD). In ALD, ROS arise from alcohol metabolism (CYP2E1 and ADH/ALDH2), causing oxidative damage and fibrosis. In NAFLD, mitochondrial dysfunction, ER stress, and lipotoxicity drive ROS overproduction due to metabolic dysregulation. Both diseases share ROS-mediated pathways, including mitochondrial/ER dysfunction, inflammation, and impaired lipid metabolism, accelerating steatosis to cirrhosis and cancer. Antioxidants, ER modulators, and lifestyle changes show therapeutic potential but require further clinical validation. Future research should leverage multi-omics and targeted therapies to optimize ROS-focused interventions for ALD and NAFLD. Full article

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

► Show Figures

Figure 1

22 pages, 10305 KiB

Open AccessArticle

Selective Dual Inhibition of TNKS1 and CDK8 by TCS9725 Attenuates STAT1/β-Catenin/TGFβ1 Signaling in Renal Cancer

by Majed Saad Al Fayi and Mishari Alshyarba

Curr. Issues Mol. Biol. 2025, 47(6), 463; https://doi.org/10.3390/cimb47060463 - 17 Jun 2025

Viewed by 317

Abstract

Background: Tankyrase (TNKS1) regulates the WNT/β-catenin pathway, while CDK8 is a transcriptional regulator overexpressed in renal cell carcinoma (RCC). This study aims to identify novel dual inhibitors of tankyrase and Cyclin-dependent kinase 8 (CDK8), utilizing bioinformatics and in vitro methods and to assess [...] Read more.

Background: Tankyrase (TNKS1) regulates the WNT/β-catenin pathway, while CDK8 is a transcriptional regulator overexpressed in renal cell carcinoma (RCC). This study aims to identify novel dual inhibitors of tankyrase and Cyclin-dependent kinase 8 (CDK8), utilizing bioinformatics and in vitro methods and to assess their efficiency in renal cancer cells. Methods: To identify leads, the ChemBridge library was screening using high-throughput virtual screening (HTVS), which was followed by protein–ligand interaction analysis, Molecular Dynamics (MD) simulation, and Gibbs binding free energy estimation. A-498, Caki-1, and HK-2 cells were employed to validate in vitro efficacy. Results: TCS9725 was discovered by HTVS with binding affinities of −8.1 kcal/mol and −8.2 kcal/mol for TNKS1 and CDK8, respectively. TCS9725 had robust binding interactions with root mean square deviation values of 0.00 nm. The ΔG binding estimate was −27.45 for TNKS1 and −27.88 for CDK8, respectively. ADME predictions favored specific small-molecule inhibition profiles. TCS9725 reduced TNKS1 and CDK8 activities with IC50s of 243 nM and 403.6 nM, respectively. The compound efficiently inhibited the growth of A-498 and Caki-1 cells with GI50 values of 385.9 nM and 243.6 nM, respectively, with high selectivity compared to the non-cancerous kidney cells. TCS9725 decreased STAT1 and β-catenin positivity in A-498 and Caki-1 cells. The compound induced apoptosis and reduced TGFβ-stimulated trans-endothelial migration and p-smad2/3 signaling in both RCC cells. Conclusions: This work provides valuable insights into the therapeutic potential of TCS9725, a dual inhibitor of TNKS1 and CDK8. Further developments of this molecule could lead to new and effective treatments for this devastating disease. Full article

(This article belongs to the Special Issue Molecular Research of Urological Diseases)

► Show Figures

Graphical abstract

20 pages, 574 KiB

Open AccessReview

The Regulatory Role of Non-Coding RNAs in Autophagy-Dependent Ischemia–Reperfusion Injury of the Brain

by Irina O. Zakharova, Liubov V. Bayunova and Natalia F. Avrova

Curr. Issues Mol. Biol. 2025, 47(6), 462; https://doi.org/10.3390/cimb47060462 - 17 Jun 2025

Viewed by 343

Abstract

In recent years, it has become clear that non-coding RNAs play an important role in regulating the development of various organs and pathological conditions, including cerebral ischemia and reperfusion. Non-coding RNAs are mainly represented by long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular [...] Read more.

In recent years, it has become clear that non-coding RNAs play an important role in regulating the development of various organs and pathological conditions, including cerebral ischemia and reperfusion. Non-coding RNAs are mainly represented by long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs). Most of the human genome is transcribed into such RNAs. Excessive activation of autophagy during cerebral ischemia and reperfusion results in autophagic neuronal death in addition to apoptotic death. This review shows that regulation occurs via the lncRNA (or circRNA)/miRNA/target protein signaling axes. A knockdown or a decrease in lncRNA level can lead to a significant increase in miRNA levels, followed by a decrease in the levels of messenger RNA (mRNA) of autophagy-related protein (ATG) and ATG protein itself. This leads to inhibition of autophagy and alleviation of brain ischemia–reperfusion injury. Changes in miRNA and mRNA levels of the target protein occur due to the presence of complementary nucleotide sequences with lncRNA and miRNA, respectively. If the target protein is not an ATG protein, neuroprotection during cerebral ischemia and reperfusion can result from both inhibition and activation of autophagy. The further study of the regulatory role of non-coding RNAs is important as it may help to counteract the effects of excessive autophagy activation and other adverse effects of ischemia–reperfusion injury Full article

(This article belongs to the Special Issue Molecular Mechanisms and Treatment of Ischemia–Reperfusion Injury)

► Show Figures

Figure 1

10 pages, 1576 KiB

Open AccessArticle

Differential Genetic Architecture of Insulin Resistance (HOMA-IR) Based on Obesity Status: Evidence from a Large-Scale GWAS of Koreans

by Ja-Eun Choi, Yu-Jin Kwon and Kyung-Won Hong

Curr. Issues Mol. Biol. 2025, 47(6), 461; https://doi.org/10.3390/cimb47060461 - 16 Jun 2025

Viewed by 350

Abstract

Insulin resistance (IR) is a key mechanism underlying type 2 diabetes mellitus and is closely associated with obesity. Although numerous genome-wide association studies (GWASs) have identified variants that influence IR-related traits, it remains unclear whether the genetic architecture of IR differs according to [...] Read more.

Insulin resistance (IR) is a key mechanism underlying type 2 diabetes mellitus and is closely associated with obesity. Although numerous genome-wide association studies (GWASs) have identified variants that influence IR-related traits, it remains unclear whether the genetic architecture of IR differs according to obesity status. We conducted a stratified GWAS of the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) in 8906 Korean individuals from the Korean Genome and Epidemiology Study. Participants were categorized into a normal-weight group (Body Mass Index (BMI) ≤ 23 kg/m²) and an overweight or obese group (BMI > 23 kg/m²), and the GWAS was performed separately within each group. No significant genome-wide variants were identified in the normal-weight group; however, seven loci showed suggestive associations. In contrast, in the overweight and obese group, two loci, rs662799 in Apolipoprotein A5 (APOA5) and rs671 in Aldehyde Dehydrogenase 2 (ALDH2), showed genome-wide significance, with seven loci showing suggestive associations. The risk allele of rs662799 was associated with increased HOMA-IR values, with a stronger effect observed in the overweight and obese group. This finding aligns with the known role of APOA5 in triglyceride metabolism, suggesting that a higher BMI may exacerbate its effect on IR. These results highlight obesity-specific genetic susceptibility to IR and the need to consider obesity status in genetic studies of metabolic traits. Full article

(This article belongs to the Special Issue Molecular Insights into Multifactorial Causes of Insulin Resistance in Obesity)

► Show Figures

Graphical abstract

48 pages, 8758 KiB

Open AccessReview

Targeting Cancer Cell Fate: Apoptosis, Autophagy, and Gold Nanoparticles in Treatment Strategies

by Maria Anthi Kouri, Alexandra Tsaroucha, Theano-Marina Axakali, Panagiotis Varelas, Vassilis Kouloulias, Kalliopi Platoni and Efstathios P. Efstathopoulos

Curr. Issues Mol. Biol. 2025, 47(6), 460; https://doi.org/10.3390/cimb47060460 - 14 Jun 2025

Viewed by 493

Abstract

At the intersection of nanotechnology and cancer biology, gold nanoparticles (AuNPs) have emerged as more than passive carriers—they are active agents capable of reshaping cellular fate. Among their most promising attributes is the potential to modulate apoptosis and autophagy, two intricately linked pathways [...] Read more.

At the intersection of nanotechnology and cancer biology, gold nanoparticles (AuNPs) have emerged as more than passive carriers—they are active agents capable of reshaping cellular fate. Among their most promising attributes is the potential to modulate apoptosis and autophagy, two intricately linked pathways that determine tumor response to stress, damage, and treatment. Apoptosis serves as the principal mechanism of programmed cell death, while autophagy offers a dualistic role—preserving survival under transient stress or contributing to cell death under sustained insult. Thus, understanding how these mechanisms interact—and how AuNPs influence this crosstalk—may be key to unlocking more effective oncologic therapies. This review explores the molecular interplay between apoptosis and autophagy in cancer and evaluates how AuNPs impact these pathways. By enhancing radiosensitization in radiation therapy and improving drug delivery and chemotherapeutic precision, AuNPs offer a unique strategy to circumvent resistance in aggressive or refractory tumors towards shaping their biological behavior and cellular pathways and, therefore, forming a patient-centered personalized therapeutic potential. Yet, clinical translation remains challenging. The dynamic physicochemical nature of AuNPs makes their biological behavior highly context-dependent. Combined with the complexity of apoptotic and autophagic signaling and tumor heterogeneity, this creates a triad of profound intricacy. However, within this complexity lies therapeutic opportunity. Framing AuNPs, apoptosis, and autophagy as a synergistic axis may enable mechanism-informed, adaptable, and patient-specific cancer therapies. This paradigm shift invites a more strategic integration of nanotechnology with molecular oncology, advancing the frontier of precision medicine. Full article

(This article belongs to the Special Issue Effects of Nanoparticles on Living Organisms, 3rd Edition)

► Show Figures

Figure 1

18 pages, 1584 KiB

Open AccessArticle

A Theoretical and Practical Analysis of Membrane Protein Genes Altered in Neutrophils in Parkinson’s Disease

by Araliz López Pintor, Miriam Nolasco López, José Daniel Lozada-Ramírez, Martín Alejandro Serrano-Meneses, Alicia Ortega Aguilar, Dante Oropeza Canto, César Flores-de los Ángeles, Victor Hugo Anaya-Muñoz and Aura Matilde Jiménez-Garduño

Curr. Issues Mol. Biol. 2025, 47(6), 459; https://doi.org/10.3390/cimb47060459 - 13 Jun 2025

Viewed by 824

Abstract

Parkinson’s disease (PD) is a major health concern, with no accurate or early diagnostic test available for most patients. Chronic inflammation is a recognized contributor to PD pathogenesis; thus, membrane proteins of inflammatory cells such as neutrophils present an accessible target for detecting [...] Read more.

Parkinson’s disease (PD) is a major health concern, with no accurate or early diagnostic test available for most patients. Chronic inflammation is a recognized contributor to PD pathogenesis; thus, membrane proteins of inflammatory cells such as neutrophils present an accessible target for detecting early molecular changes. In this study, we conducted a theoretical analysis using the GSE99039 database to identify differentially expressed genes (DEGs) in leukocytes from PD patients. From this, we selected nine top candidates for digital polymerase chain reaction (dPCR) analysis in isolated neutrophils from nine PD patients and nine matched controls. Our results revealed significant upregulation of ORAI3 and CLCN2. Unexpectedly, both ACTB (β-actin) and SNCA (alpha-synuclein) were also upregulated in neutrophils. Notably, this study provides the first evidence of CLCN2 expression in neutrophils and demonstrates the significant upregulation of four genes via dPCR. These genes may serve as potential biomarkers for future research on PD detection. Full article

(This article belongs to the Special Issue The Role of Neuroinflammation in Neurodegenerative Diseases)

► Show Figures

Figure 1

13 pages, 675 KiB

Open AccessArticle

HLA-DRB1 and DQB1 Allelic Polymorphism and Multiple Sclerosis in a Moroccan Population

by Abir Fguirouche, Yahya Naji, Morad Guennouni, Raja Hazime, Safa Zahlane, Mohamed Chraa, Najib Kissani, Nissrine Louhab and Brahim Admou

Curr. Issues Mol. Biol. 2025, 47(6), 458; https://doi.org/10.3390/cimb47060458 - 13 Jun 2025

Viewed by 450

Abstract

Introduction: Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system (CNS) that leads to inflammation and demyelination, manifesting in either a relapsing–remitting or progressive form. As a multifactorial disease, MS involves both genetic and environmental factors, with a [...] Read more.

Introduction: Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system (CNS) that leads to inflammation and demyelination, manifesting in either a relapsing–remitting or progressive form. As a multifactorial disease, MS involves both genetic and environmental factors, with a known significant contribution from human leukocyte antigen (HLA) genes, mainly represented by the HLA-DRB1 and HLA-DQB1 loci, which have been linked to either susceptibility or protection, but variably across populations and ethnic groups. We aimed to study the distribution and polymorphism of HLA-DRB1 and HLA-DQB1 alleles in a population with MS from the southern Moroccan region, in comparison with healthy controls. Materials and Methods: A cross-sectional study was conducted over a period of 2 years (2022–2024) in a MS cohort including 40 patients and 100 healthy controls. DRB1 and DQB1 HLA genotyping was performed using a high-resolution reverse sequence-specific oligonucleotide (SSO) method, based on the Luminex system (xMAP technology, One lambda^®). Data were analyzed using SPSS 26; differences in allele frequencies were evaluated by the Chi-square test and Fisher’s exact test. OR (95% CI) was calculated, and FDR corrections were applied for multiple testing. Results: Among the various HLA-DRB1 and DQB1 alleles studied, including those considered as predisposing to MS, the DQB1*02:01 and DRB1*15:01 alleles were more prevalent in MS patients, with 40% and 8.8% vs. 16% and 4.08% in controls respectively, although these differences were not statistically significant (p = 0.06 and p = 0.12). Likewise, the DRB1*15:01-DQB1*06:02 association was significantly more prevalent in the MS group (9%, p = 0.004). In contrast, the DRB1*07:01 allele, linked to protection against MS in many populations, was significantly predominant in controls (17%, p = 0.004). Similarly, the DRB1*07:01–DQB*02:01 combination was rather more frequent in controls (12%, p = 0.01). Confronted to MS clinical forms, we remarkably noted that the DRB1*13:03 allele was found only among relapsing–remitting MS (RRMS) patients (6%, p = 0.003), while DQB1*02:01 was significantly associated with RRMS (42.1%) and primary progressive MS (41%, p = 0.001), with an intermediate Expanded Disability Status Scale (EDSS) score, which may indicate a possible link with disease progression and severity. Conclusions: The results of our study highlighted particular HLA alleles, DRB1 and DQB1, alone or in combination, as potential immunogenic factors of susceptibility to MS in a population from southern Morocco, while other alleles seem rather to protect against the disease. This HLA polymorphism is also reflected in the clinical forms of the disease, showing a tendency toward severity for certain alleles. However, such preliminary results need to be consolidated and confirmed by studies carried out on a larger population sample, and compared with others on a national scale. Full article

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

► Show Figures

Figure 1

13 pages, 11396 KiB

Open AccessArticle

Morphometric and Enzymatic Changes in Gills of Rainbow Trout After Exposure to Suboptimal Low Temperature

by Elias Lahnsteiner, Nooshin Zamannejad, Anna Dünser and Franz Lahnsteiner

Curr. Issues Mol. Biol. 2025, 47(6), 457; https://doi.org/10.3390/cimb47060457 - 13 Jun 2025

Viewed by 530

Abstract

The present study investigated the influence of a 30 day exposure of rainbow trout (Oncorhynchus mykiss) to a suboptimal low temperature of 1.8 ± 1.0 °C on their different gill characteristics (morphometry, enzyme activities, and expression of genes) in comparison to [...] Read more.

The present study investigated the influence of a 30 day exposure of rainbow trout (Oncorhynchus mykiss) to a suboptimal low temperature of 1.8 ± 1.0 °C on their different gill characteristics (morphometry, enzyme activities, and expression of genes) in comparison to fish acclimated to 9.4 ± 0.1 °C. Morphometric analysis revealed a significant decrease in the distance between the secondary lamellae at the low temperature, which can be interpreted as a decrease in the effective gill surface. The epithelial thickness increased at the lower temperatures, which is considered a mechanism to reduce ion fluxes and save the energy costs for osmoregulation. The length of the primary lamellae, distance between the primary lamellae, length of the secondary lamellae, as well as the number of mucus cells, chloride cells, and capillaries per mm of the secondary lamella were similar between the temperature regimes. The enzymatic activities of pyruvate kinase and malate dehydrogenase were significantly increased in cold-exposed fish, whereas lactate dehydrogenase activity was higher in controls, indicating increased energy expenditure and adjustments in energy metabolism. The activities of carbonic anhydrase, caspase, Na⁺/K⁺ ATPase, and H⁺ ATPase, and the gene expressions of hif1a, ca2, rhCG, slc26a6, and slc9a1 showed no statistically significant differences between the two temperature regimes. Therefore, it can be concluded that ammonia transport, acid–base regulation, and osmoregulation were not affected by the tested low temperature regime. These findings highlight that exposure to suboptimal temperatures induces structural and metabolic modifications in rainbow trout gills, potentially as an adaptive response to thermal stress. This study contributes to the understanding of fish acclimation to cold environments, with implications for aquaculture and ecological resilience in changing climates. Full article

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

► Show Figures

Figure 1

19 pages, 489 KiB

Open AccessReview

Natural Bioactive Compounds in Sheep Milk: Potential Biomedical Applications

by Zuzanna Flis, Edyta Molik, Anna Ptak and Piotr Szatkowski

Curr. Issues Mol. Biol. 2025, 47(6), 456; https://doi.org/10.3390/cimb47060456 - 12 Jun 2025

Viewed by 774

Abstract

Sheep milk is a rich source of bioactive compounds with significant potential in functional foods and biomedical applications. It contains high levels of proteins, peptides, and fatty acids with numerous health-promoting properties for the human body. Key components such as lactoferrin, proline, orotic [...] Read more.

Sheep milk is a rich source of bioactive compounds with significant potential in functional foods and biomedical applications. It contains high levels of proteins, peptides, and fatty acids with numerous health-promoting properties for the human body. Key components such as lactoferrin, proline, orotic acid, and conjugated linoleic acid (CLA) support the prevention and treatment of chronic diseases such as diabetes, cardiovascular disease, obesity, cancer, and neurodegenerative disorders. Bioactive peptides from sheep milk regulate blood glucose levels by inhibiting enzymes such as dipeptidyl peptidase-IV (DPP-IV) and α-glucosidase, while conjugated linoleic acid improves lipid metabolism and reduces inflammation. The high-quality proteins in sheep milk are essential for tissue regeneration and maintaining muscle mass, which is particularly beneficial for the elderly and infants who are allergic to cow milk. Recently, there has been an increasing interest in hydrogel dressings enriched with bioactive substances from sheep milk, which support wound healing by supporting collagen synthesis, reducing inflammation, and having antimicrobial properties. Such hydrogels are particularly promising for the treatment of chronic wounds, burns, and diabetic ulcers, making them a valuable tool in regenerative medicine. The aim of this manuscript is to review the current reports on bioactive components of sheep milk and their potential for biomedical applications. Full article

(This article belongs to the Special Issue Natural Product Drug Activity and Biomedicine Application)

► Show Figures

Figure 1

13 pages, 2481 KiB

Open AccessArticle

Chronic Exposure of Renal Progenitor Cells (HRTPT) to As (III) Implicates Microfibril Associated Protein 5 (MFAP5) in the Activation of Carcinoembryonic Antigen Related Cell Adhesion Molecules (CEACAM 5 and 6)

by Md Ehsanul Haque, Donald A. Sens and Scott H. Garrett

Curr. Issues Mol. Biol. 2025, 47(6), 455; https://doi.org/10.3390/cimb47060455 - 12 Jun 2025

Viewed by 377

Abstract

Studies on populations exposed to inorganic arsenic (iAs) have shown an association with the development of chronic kidney disease (CKD) and renal cell carcinoma (RCC). However, there are few studies addressing how acute exposure of the human kidney to iAs might lead to [...] Read more.

Studies on populations exposed to inorganic arsenic (iAs) have shown an association with the development of chronic kidney disease (CKD) and renal cell carcinoma (RCC). However, there are few studies addressing how acute exposure of the human kidney to iAs might lead to the long-term alterations that might lead to CKD or RCC. This laboratory’s hypothesis is that renal exposure to iAs might alter the renal cells responsible for the repair and regeneration of nephrons damaged by iAs exposure or other renal toxicants. The kidney possesses a minority epithelial cell population that co-expresses PROM1 and CD24, which are believed to be involved in renal epithelial cell repair. The purpose of this work is to understand the pathogenesis of CKD in renal cortical epithelial cells. Our model consists of acute and chronic exposure of i-As (III) to “Human Renal Tubular Precursor TERT” (HRTPT). The microarray and gene validation study demonstrated a sudden induction of microfibril associated protein 5 (MFAP5) and carcinoembryonic antigen related cell adhesion molecule 5 and 6 (CEACAM 5 and 6) in chronic i-As (III)-exposed cells. Chronically exposed cells also exhibited an induction of the pAKT/AKT pathway and SOX9 transcription factor. The targeting of MFAP5 and CEACAM 5/6 could, therefore, provide a potential therapeutic approach to CKD. Full article

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

► Show Figures

Figure 1

19 pages, 414 KiB

Open AccessReview

Development of CDK4/6 Inhibitors in Gastrointestinal Cancers: Biomarkers to Move Forward

by Ioannis A. Voutsadakis

Curr. Issues Mol. Biol. 2025, 47(6), 454; https://doi.org/10.3390/cimb47060454 - 12 Jun 2025

Viewed by 655

Abstract

Targeting the cell cycle has become a focus of cancer research bearing impressive results with the introduction of CDK4/6 inhibitors in the treatment of ER-positive/HER2-negative breast cancers. However, no definitive benefit in other cancers has been observed. In gastrointestinal cancers, despite preclinical studies [...] Read more.

Targeting the cell cycle has become a focus of cancer research bearing impressive results with the introduction of CDK4/6 inhibitors in the treatment of ER-positive/HER2-negative breast cancers. However, no definitive benefit in other cancers has been observed. In gastrointestinal cancers, despite preclinical studies pinpointing positive effects on cancer inhibition in pre-clinical models, no positive clinical trials have been published with CDK4/6 inhibitors. Several biomarkers have been proposed in breast cancers, where the field is more advanced, and include up-regulations of the inhibited kinases CDK4 and CDK6 and their partner cyclin D as well as the main target of phosphorylation, RB. Up-regulation of Cyclin E, an E2F1/RB regulated gene, also arises as a marker of CDK4/6 inhibition resistance. Signaling from receptor tyrosine kinase pathways through KRAS/BRAF/MEK and PI3K/AKT/mTOR are also implicated in feedback CDK4/6 activation and inhibitors resistance. In gastrointestinal cancers, some of these biomarkers have also proven valuable in predicting sensitivity to CDK4/6 inhibitors and would lead markers to guide clinical development. Modulation of the tumor microenvironment, where immune cells are prominent components, arises as a feature of CDK4/6 inhibition and could be harnessed in therapeutic combinations. Full article

(This article belongs to the Special Issue Future Challenges of Targeted Therapy of Cancers: 2nd Edition)

► Show Figures

Figure 1

13 pages, 1292 KiB

Open AccessArticle

Miyako Bidens pilosa Extract Ameliorates Allodynia and Suppresses Spinal Microglial Activation in Mice with Partial Sciatic Nerve Ligation

by Ai Takahashi, Hiroko Miyagishi, Komugi Tsuruta, Hiroshi Nango, Dai Hirose, Yuri Aono, Minoru Tanigawa, Katsushi Nishimura, Minoru Saito, Takayuki Kawato, Tadashi Saigusa and Yasuhiro Kosuge

Curr. Issues Mol. Biol. 2025, 47(6), 453; https://doi.org/10.3390/cimb47060453 - 12 Jun 2025

Viewed by 479

Abstract

Neuropathic pain, characterized by chronic allodynia, remains difficult to manage with current pharmacotherapies. Microglial activation plays a pivotal role in the development and maintenance of neuropathic pain and represents a promising therapeutic target. We previously demonstrated that Miyako Bidens pilosa extract powder (MBP), [...] Read more.

Neuropathic pain, characterized by chronic allodynia, remains difficult to manage with current pharmacotherapies. Microglial activation plays a pivotal role in the development and maintenance of neuropathic pain and represents a promising therapeutic target. We previously demonstrated that Miyako Bidens pilosa extract powder (MBP), derived from Miyako Island, Okinawa, suppresses glial activation in a mouse model of amyotrophic lateral sclerosis. In this study, we investigated the analgesic potential of MBP in a mouse model of neuropathic pain. Neuropathic pain was induced in male ICR mice by partial sciatic nerve ligation (PSNL). Mice were orally administered MBP (2 g/kg) or vehicle daily. Mechanical allodynia was assessed using von Frey filaments. On postoperative day 7, MBP-treated mice exhibited significantly reduced allodynia compared to vehicle-treated mice. MBP also attenuated thermal hyperalgesia on postoperative day 7. Lumbar spinal cords (L5) were subjected to immunohistochemical analysis for ionized calcium-binding adaptor molecule 1 (Iba1), a microglial marker. MBP significantly decreased the number of Iba1-positive microglia in the ipsilateral dorsal horn. These results suggest that MBP alleviates neuropathic pain, at least in part, by suppressing microglial activation in the spinal cord. MBP may represent a novel plant-derived therapeutic candidate for treating neuropathic pain. Full article

(This article belongs to the Special Issue Molecular Mechanisms in Demyelinating Disorders and Remyelination Strategies of the CNS)

► Show Figures

Figure 1

21 pages, 329 KiB

Open AccessReview

Early Molecular Diagnosis and Comprehensive Treatment of Oral Cancer

by Po-Chih Hsu, Jen-Hsuan Huang, Chung-Che Tsai, Ya-Hsuan Lin and Chan-Yen Kuo

Curr. Issues Mol. Biol. 2025, 47(6), 452; https://doi.org/10.3390/cimb47060452 - 12 Jun 2025

Viewed by 492

Abstract

Oral squamous cell carcinoma (OSCC), a major subtype of head and neck squamous cell carcinoma (HNSCC), is a significant global health burden owing to its late-stage diagnosis and poor prognosis. Recent advancements in molecular biology, genomics, and imaging have transformed the landscape of [...] Read more.

Oral squamous cell carcinoma (OSCC), a major subtype of head and neck squamous cell carcinoma (HNSCC), is a significant global health burden owing to its late-stage diagnosis and poor prognosis. Recent advancements in molecular biology, genomics, and imaging have transformed the landscape of OSCC diagnosis and treatment. This review provides a comprehensive synthesis of early molecular diagnostic strategies, including biomarker discovery using next-generation sequencing, liquid biopsy, and salivary exosomal microRNAs. In addition, we highlight the emerging role of non-invasive optical imaging technologies and their clinical integration for improved surgical precision and early lesion detection. This review also discusses evolving therapeutic approaches, including immunotherapy, neoadjuvant chemotherapy, and patient-centered multimodal regimens tailored through molecular profiling. We emphasized balancing therapeutic efficacy with the quality of life in patients undergoing chemoradiotherapy. The convergence of multi-omics, artificial intelligence, and precision medicine holds promise for revolutionizing early detection and personalized treatment of OSCC, ultimately improving patient survival and clinical outcomes. Full article

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

► Show Figures

Graphical abstract

18 pages, 5811 KiB

Open AccessArticle

Investigating the Effects of ONC206 Alone and in Combination with Cisplatin on Ovarian Cancer Cell Models

by Sara Mikhael, Rona Fayyad, Leen Abi Harfouch, Varun Vijay Prabhu, Hisham F. Bahmad, Wassim Abou-Kheir and Georges Daoud

Curr. Issues Mol. Biol. 2025, 47(6), 451; https://doi.org/10.3390/cimb47060451 - 12 Jun 2025

Viewed by 406

Abstract

Ovarian cancer (OC) is the most lethal gynecologic malignancy worldwide, with high rates of disease relapse posing a significant therapeutic challenge. Consequently, there is an urgent need to develop novel treatments for OC. This study aims to evaluate the effects of the novel [...] Read more.

Ovarian cancer (OC) is the most lethal gynecologic malignancy worldwide, with high rates of disease relapse posing a significant therapeutic challenge. Consequently, there is an urgent need to develop novel treatments for OC. This study aims to evaluate the effects of the novel imipridone, ONC206, both as a monotherapy and in combination with the standard of care chemotherapy drug, cisplatin (CDDP), on human OC cell lines. In order to study the effect of ONC206 and CDDP on ovarian cancer, two cell lines, OVCAR-420 and SKOV-3, were used in this study. Cell proliferation was assessed using MTT assay while cell viability was evaluated using the trypan blue exclusion assay. Cell migration was examined using the wound healing assay. To investigate the effects of both treatments, alone or in combination on the stem-cell-like population of OC cells, the sphere-forming assay was employed. Our results revealed that ONC206, alone or in combination with CDDP, exerts a potent anti-proliferative effect on both OVCAR-420 and SKOV-3 cells, as shown in the MTT and trypan blue exclusion assays. Interestingly, a synergistic effect was observed when ONC206 was combined with CDDP, enhancing the overall anti-cancer efficacy. Additionally, ONC206 alone or in combination with CDDP inhibited the migratory ability of the ovarian cancer cells. Furthermore, the activity of ovarian cancer stem cells was inhibited when cells were treated with ONC206 alone or in combination with CDDP, as shown in the significant decrease in both the size and the sphere-forming ability of ovarian cancer stem cells in the 3D culture model. Our results highly suggest the potential of imipridones as a new class of therapeutics in ovarian cancer management. Among these, ONC206 shows nanomolar potency, highlighting its potential as a standalone therapy or in combination with existing treatment regimens. Full article

(This article belongs to the Special Issue Advances in Pharmacotherapeutic Strategies to Prevent Tumor Development, Progression and Treatment Resistance, 2nd Edition)

► Show Figures

Figure 1

19 pages, 11778 KiB

Open AccessArticle

Lipid-Lowering Potential of Almond Hulls (Quercetin, Baicalein, and Kaempferol): Insights from Network Pharmacology and Molecular Dynamics

by Qiming Miao, Lu Sun, Jiayuan Wu, Xinyue Zhu, Juer Liu, Roger Ruan, Guangwei Huang, Shengquan Mi and Yanling Cheng

Curr. Issues Mol. Biol. 2025, 47(6), 450; https://doi.org/10.3390/cimb47060450 - 12 Jun 2025

Viewed by 461

Abstract

The advancement of modern lifestyles has precipitated excessive consumption of energy-dense foods, driving the escalating global burden of lipid metabolism dysregulation-related pathologies—including obesity, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and cardiovascular disorders—which collectively pose a formidable challenge to global [...] Read more.

The advancement of modern lifestyles has precipitated excessive consumption of energy-dense foods, driving the escalating global burden of lipid metabolism dysregulation-related pathologies—including obesity, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and cardiovascular disorders—which collectively pose a formidable challenge to global public health systems. The almond hull, as a by-product of almond processing, is rich in polyphenolic compounds with demonstrated antioxidant, anti-inflammatory, and lipid-lowering potential, though its precise hypo-lipidemic mechanisms remain elusive. In this study, polyphenols were extracted from almond hulls using 50% ethanol with ultrasound-assisted extraction, followed by preliminary purification via solvent partitioning. The ethyl acetate fraction was analyzed by liquid chromatography–mass spectrometry (LC-MS). Network pharmacology and molecular docking were employed to investigate the interactions between key bioactive constituents (e.g., quercetin, baicalein, and kaempferol) and targets in lipid metabolism-related pathways. Molecular dynamics (MD) simulations further evaluated the stability of the lowest-energy complexes. Results revealed that the ethyl acetate fraction exhibited potent pancreatic lipase inhibitory activity (IC50 = 204.2 µg/mL). At 0.1 mg/mL after 24 h treatment, it significantly reduced free fatty acids (FFAs)-induced intracellular triglyceride accumulation (p < 0.01) and enhanced cellular antioxidant capacity. Network pharmacology and in vitro studies suggest almond hull extract modulates PI3K-AKT signaling and improves insulin resistance, demonstrating lipid-lowering effects. These findings support its potential in functional foods and pharmaceuticals, though further in vivo validation and mechanistic investigations are required. Full article

(This article belongs to the Section Molecular Pharmacology)

► Show Figures

Figure 1

20 pages, 7711 KiB

Open AccessArticle

Preliminary Analysis of the Salt-Tolerance Mechanisms of Different Varieties of Dandelion (Taraxacum mongolicum Hand.-Mazz.) Under Salt Stress

by Wei Feng, Ran Meng, Yue Chen, Zhaojia Li, Xuelin Lu, Xiuping Wang and Zhe Wu

Curr. Issues Mol. Biol. 2025, 47(6), 449; https://doi.org/10.3390/cimb47060449 - 11 Jun 2025

Viewed by 403

Abstract

Soil salinization hinders plant growth and agricultural production, so breeding salt-tolerant crops is an economical way to exploit saline–alkali soils. However, the specific metabolites and associated pathways involved in salt tolerance of the dandelion have not been clearly elucidated so far. Here, we [...] Read more.

Soil salinization hinders plant growth and agricultural production, so breeding salt-tolerant crops is an economical way to exploit saline–alkali soils. However, the specific metabolites and associated pathways involved in salt tolerance of the dandelion have not been clearly elucidated so far. Here, we compared the transcriptome and metabolome responses of 0.7% NaCl-stressed dandelion ‘BINPU2’ (variety A) and ‘TANGHAI’ (variety B). Our results showed that 222 significantly altered metabolites mainly enriched in arginine biosynthesis and pyruvate metabolism according to a KEGG database analysis in variety A, while 147 differential metabolites were predominantly enriched in galactose metabolism and the pentose phosphate pathway in variety B. The transcriptome data indicated that the differentially expressed genes (DEGs) in variety A were linked to secondary metabolite biosynthesis, phenylpropanoid biosynthesis, and photosynthesis–antenna proteins. Additionally, KEGG annotations revealed the DEGs had functions assigned to general function prediction only, post-translation modification, protein turnover, chaperones, and signal transduction mechanisms in variety A. By contrast, the DEGs had functions assigned to variety B as plant–pathogen interactions, phenylpropanoid biosynthesis, and photosynthesis–antenna proteins, including general function prediction, signal transduction mechanisms, and secondary metabolite biosynthesis from the KOG database functional annotation. Furthermore, 181 and 162 transcription factors (TFs) expressed under saline stress conditions specifically were detected between varieties A and B, respectively, representing 36 and 37 TF families. Metabolomics combined with transcriptomics revealed that salt stress induced substantial changes in terpenoid metabolites, ubiquinone biosynthesis metabolites, and pyruvate metabolites, mediated by key enzymes from the glycoside hydrolase family, adenylate esterases family, and P450 cytochrome family at the mRNA and/or metabolite levels. These results may uncover the potential salt-response mechanisms in different dandelion varieties, providing insights for breeding salt-tolerant crop plants suitable for saline–alkali land cultivation. Full article

(This article belongs to the Section Molecular Plant Sciences)

► Show Figures

Figure 1

10 pages, 1593 KiB

Open AccessArticle

Comparative Analysis of Mitochondrial Genome from Phormictopus cancerides (Arachnida: Theraphosidae) with Phylogenetic Implications

by Hongjian Chen, Wei Xu, Hongyi Liu, Yiwen Yang and Ming Gao

Curr. Issues Mol. Biol. 2025, 47(6), 448; https://doi.org/10.3390/cimb47060448 - 11 Jun 2025

Viewed by 391

Abstract

Tarantulas represent a highly diverse taxonomic group and play a crucial role in ecosystems. To gain a deeper understanding of the evolutionary relationships within the family Theraphosidae, in this study, we characterized the mitochondrial genome (mitogenome) of Phormictopus cancerides for the first time. [...] Read more.

Tarantulas represent a highly diverse taxonomic group and play a crucial role in ecosystems. To gain a deeper understanding of the evolutionary relationships within the family Theraphosidae, in this study, we characterized the mitochondrial genome (mitogenome) of Phormictopus cancerides for the first time. The mitogenome is a typical circular double-stranded molecule, with a size of 13,776 bp. P. cancerides exhibited an A/T nucleotide preference (61.9–68.5% A + T content), with their rRNAs and tRNAs showing higher values than PCGs and the CR. The genes and the gene order were consistent with other Theraphosidae mitogenomes. The mitogenome was compacted and showed a bias for A/T. Ka/Ks analyses showed that the ND3 gene had the highest evolutionary rate, while the COX1 gene displayed a relatively slower evolution. Our phylogenetic analysis based on mitogenomes showed the subfamily Theraphosinae is closely related to the subfamily Harpactirinae and the subfamily Selenocosmiinae. Our results could contribute to the study of relationships within the family Theraphosidae and lay the foundation for further studies on tarantulas. Full article

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

► Show Figures

Figure 1

34 pages, 826 KiB

Open AccessReview

The Application of Microsatellite Markers as Molecular Tools for Studying Genomic Variability in Vertebrate Populations

by Roman O. Kulibaba, Kornsorn Srikulnath, Worapong Singchat, Yuriy V. Liashenko, Darren K. Griffin and Michael N. Romanov

Curr. Issues Mol. Biol. 2025, 47(6), 447; https://doi.org/10.3390/cimb47060447 - 11 Jun 2025

Viewed by 468

Abstract

Vertebrate molecular genetic research methods typically employ single genetic loci (monolocus markers) and those involving a variable number of loci (multilocus markers). The former often employ microsatellites that ensure accuracy in establishing inbreeding, tracking pan-generational dynamics of genetic parameters, assessing genetic purity, and [...] Read more.

Vertebrate molecular genetic research methods typically employ single genetic loci (monolocus markers) and those involving a variable number of loci (multilocus markers). The former often employ microsatellites that ensure accuracy in establishing inbreeding, tracking pan-generational dynamics of genetic parameters, assessing genetic purity, and facilitating genotype/phenotype correlations. They also enable the determination and identification of unique alleles by studying and managing marker-assisted breeding regimes to control the artificial selection of agriculturally important traits. Microsatellites consist of 2–6 nucleotides that repeat numerous times and are widely distributed throughout genomes. Their main advantages lie in their ease of use for PCR amplification, their known genome localization, and their incredible polymorphism (variability) levels. Robust lab-based molecular technologies are supplemented by high-quality statistics and bioinformatics and have been widely employed, especially in those instances when more costly, high throughput techniques are not available. Here, we consider that human and livestock microsatellite studies have been a “roadmap” for the genetics, breeding, and conservation of wildlife and rare animal breeds. In this context, we examine humans and other primates, cattle and other artiodactyls, chickens and other birds, carnivores (cats and dogs), elephants, reptiles, amphibians, and fish. Studies originally designed for mass animal production have thus been adapted to save less abundant species, highlighting the need for molecular scientists to consider where research may be applied in different disciplines. Full article

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

► Show Figures

Figure 1

Journal Menu

Journal Browser

Curr. Issues Mol. Biol., Volume 47, Issue 6 (June 2025) – 93 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI