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Current Issues in Molecular Biology

Current Issues in Molecular Biology is an international, scientific, peer-reviewed, open access journal on molecular biology, published monthly online by MDPI (from Volume 43 Issue 1-2021).

Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
High Visibility: indexed within Scopus, SCIE (Web of Science), PMC, PubMed, Embase, CAPlus / SciFinder, FSTA, AGRIS, and other databases.
Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 17.8 days after submission; acceptance to publication is undertaken in 2.7 days (median values for papers published in this journal in the first half of 2025).
Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names are published annually in the journal.

Impact Factor: 3.0 (2024); 5-Year Impact Factor: 3.2 (2024)

Imprint Information Journal Flyer Open Access ISSN: 1467-3045

Latest Articles

28 pages, 2732 KiB

Open AccessReview

Molecular Mechanisms of Radiation Resistance in Breast Cancer: A Systematic Review of Radiosensitization Strategies

by Emma Mageau, Ronan Derbowka, Noah Dickinson, Natalie Lefort, A. Thomas Kovala, Douglas R. Boreham, T. C. Tai, Christopher Thome and Sujeenthar Tharmalingam

Curr. Issues Mol. Biol. 2025, 47(8), 589; https://doi.org/10.3390/cimb47080589 - 24 Jul 2025

Breast cancer remains one of the most prevalent malignancies worldwide, and radiation therapy is a central component of its management. However, intrinsic or acquired resistance to radiation significantly compromises therapeutic efficacy. This systematic review aimed to identify and evaluate molecular mechanisms and interventions [...] Read more.

Breast cancer remains one of the most prevalent malignancies worldwide, and radiation therapy is a central component of its management. However, intrinsic or acquired resistance to radiation significantly compromises therapeutic efficacy. This systematic review aimed to identify and evaluate molecular mechanisms and interventions that influence radiation sensitivity in breast cancer models. A comprehensive PubMed search was conducted using the terms “breast cancer” and “radiation resistance” for studies published between 2002 and 2024. Seventy-nine eligible studies were included. The most frequently investigated mechanisms included the dysregulation of the PI3K/AKT/mTOR and MAPK signaling pathways, enhanced DNA damage repair via non-homologous end joining (NHEJ), and the overexpression of cancer stem cell markers such as CD44⁺/CD24⁻/low and ALDH1. Several studies highlighted the role of non-coding RNAs, particularly the lncRNA DUXAP8 and microRNAs such as miR-21, miR-144, miR-33a, and miR-634, in modulating radiation response. Components of the tumor microenvironment, including cancer-associated fibroblasts and immune regulators, also contributed to radiation resistance. By synthesizing current evidence, this review provides a consolidated resource to guide future mechanistic studies and therapeutic development. This review highlights promising molecular targets and emerging strategies to enhance radiosensitivity and offers a foundation for translational research aimed at improving outcomes in radiation-refractory breast cancer. Full article

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

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9 pages, 635 KiB

Open AccessArticle

Osteogenic Potential of Osteolforte: Gene and Protein-Level Evaluation in Human Bone Marrow Stromal Cells

by Da-Sol Kim, Soo-Kyung Bae, Yeon-Ju Kwak, Geum-Joung Youn and Hye-Ock Jang

Curr. Issues Mol. Biol. 2025, 47(8), 588; https://doi.org/10.3390/cimb47080588 - 24 Jul 2025

Osteolforte, a compound with potential bone-regenerative properties, was investigated for its effects on human bone marrow stromal cells (hBMSCs). This study aimed to evaluate its impact on cell viability, osteogenic differentiation, and both gene and protein expression using a combination of assays, [...] Read more.

Osteolforte, a compound with potential bone-regenerative properties, was investigated for its effects on human bone marrow stromal cells (hBMSCs). This study aimed to evaluate its impact on cell viability, osteogenic differentiation, and both gene and protein expression using a combination of assays, including CCK-8, Alizarin Red S staining, Quantitative Real-Time PCR (qRT-PCR), and Western blot analysis. The results demonstrated that Osteolforte significantly enhanced osteogenic differentiation in hBMSCs. Alizarin Red S staining revealed increased mineralization, indicating elevated calcium deposition. Gene expression analysis showed an upregulation of key osteogenic markers, including runt-related transcription factor-2 (RUNX-2), collagen type I (COL-1), and bone morphogenetic protein-2 (BMP-2), supporting the role of Osteolforte in promoting osteoblastic activity. In particular, the elevated expression of RUNX-2—a master transcription factor in osteoblast differentiation along with COL-1, a major bone matrix component, and BMP-2, a key bone morphogenetic protein—highlights the compound’s osteogenic potential. In conclusion, Osteolforte enhances early-stage osteogenesis and mineralization in hBMSCs and represents a promising candidate for bone regeneration. Full article

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

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11 pages, 2454 KiB

Open AccessCommunication

Effect of a Novel Antidepressant and Anticancer Nuc01 on Depression in Cancer Survivors

by Changchun Yuan, Xudong Shi, Zhiqiang Wang, Yuqiang Li, Wenbing Ma and Kai Fu

Curr. Issues Mol. Biol. 2025, 47(8), 587; https://doi.org/10.3390/cimb47080587 - 24 Jul 2025

Depression in cancer survivors is commonly treated with serotonin and norepinephrine reuptake inhibitors (SNRIs), such as venlafaxine. These drugs alleviate depressive symptoms by inhibiting the reuptake of serotonin and norepinephrine. However, a novel approach has emerged with the development of trans-2-phenylcyclopropylamine (PCPA)–drug [...] Read more.

Depression in cancer survivors is commonly treated with serotonin and norepinephrine reuptake inhibitors (SNRIs), such as venlafaxine. These drugs alleviate depressive symptoms by inhibiting the reuptake of serotonin and norepinephrine. However, a novel approach has emerged with the development of trans-2-phenylcyclopropylamine (PCPA)–drug conjugates that inhibit lysine-specific demethylase 1 (LSD1), which is a biomarker and molecular target for cancer therapy. LSD1 inhibition can effectively suppress cancer cell proliferation. Nuc01 is a novel PCPA–drug conjugate designed as a prodrug of venlafaxine. In vivo studies showed that Nuc01 dose-dependently reduced immobility time in the tail suspension test in mice, outperforming desmethylvenlafaxine. This suggests that Nuc01 may act as a potent triple reuptake inhibitor, potentially offering enhanced efficacy in the treatment of depression. Additionally, in vitro studies demonstrated that Nuc01 effectively occupies the PCPA binding site within LSD1 (IC₅₀ = 530 nm) and inhibits the proliferation of MDA-MB-231 cancer cells (IC₅₀ = 1130 nm). These findings suggest that Nuc01 may function as an LSD1 inhibitor with potential anticancer properties. Collectively, the data indicate that Nuc01 appears to exhibit dual functional characteristics: acting as a triple reuptake inhibitor potentially applicable for depression treatment and as an LSD1 inhibitor demonstrating anticancer potential. Full article

(This article belongs to the Section Molecular Medicine)

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18 pages, 968 KiB

Open AccessReview

IL-4 and Brentuximab Vedotin in Mycosis Fungoides: A Perspective on Potential Therapeutic Interactions and Future Research Directions

by Mihaela Andreescu, Sorin Ioan Tudorache, Cosmin Alec Moldovan and Bogdan Andreescu

Curr. Issues Mol. Biol. 2025, 47(8), 586; https://doi.org/10.3390/cimb47080586 - 24 Jul 2025

Background: Mycosis fungoides (MF), the most prevalent cutaneous T cell lymphoma, features clonal CD4⁺ T cell proliferation within a Th2-dominant microenvironment. Interleukin-4 (IL-4) promotes disease progression while Brentuximab Vedotin (BV), an anti-CD30 antibody–drug conjugate, shows efficacy but faces resistance challenges. Methods: We conducted [...] Read more.

Background: Mycosis fungoides (MF), the most prevalent cutaneous T cell lymphoma, features clonal CD4⁺ T cell proliferation within a Th2-dominant microenvironment. Interleukin-4 (IL-4) promotes disease progression while Brentuximab Vedotin (BV), an anti-CD30 antibody–drug conjugate, shows efficacy but faces resistance challenges. Methods: We conducted a narrative literature review (2010–2024) synthesizing evidence on IL-4 signaling and BV’s efficacy in MF to develop a theoretical framework for combination therapy. Results: IL-4 may modulate CD30 expression and compromise BV’s effectiveness through immunosuppressive microenvironment remodeling. Theoretical mechanisms suggest that IL-4 pathway inhibition could reprogram the microenvironment toward Th1 dominance and restore BV sensitivity. However, no direct experimental evidence validates this combination, and safety concerns including potential disease acceleration require careful evaluation. Conclusions: The proposed IL-4/BV combination represents a biologically compelling but unproven hypothesis requiring systematic preclinical validation and biomarker-driven clinical trials. This framework could guide future research toward transforming treatment approaches for CD30-positive MF by targeting both malignant cells and their immunologically permissive microenvironment. Full article

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

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11 pages, 254 KiB

Open AccessArticle

New Tool Against Tuberculosis: The Potential of the LAMP Lateral Flow Assay in Resource-Limited Settings

by Marisol Rosas-Diaz, Carmen Palacios-Reyes, Ricardo Godinez-Aguilar, Deyanira Escalante-Bautista, Laura Alfaro Hernández, Ana P. Juarez-Islas, Patricia Segundo-Ibañez, Gabriela Salas-Cuevas, Ángel Olvera-Serrano, Juan Carlos Hernandez-Martinez, Victor Hugo Ramos-Garcia, Esperanza Milagros Garcia Oropesa, Omar Flores-García, Jose Luis Galvez-Romero, Griselda León Burgoa and Manuel Nolasco-Quiroga

Curr. Issues Mol. Biol. 2025, 47(8), 585; https://doi.org/10.3390/cimb47080585 - 23 Jul 2025

Tuberculosis (TB) is a global public health issue requiring early and accurate diagnosis. The loop-mediated isothermal amplification (LAMP) assay is a promising alternative recommended by the WHO for the initial diagnosis of pulmonary TB, particularly in resource-limited settings. This study evaluated the sensitivity [...] Read more.

Tuberculosis (TB) is a global public health issue requiring early and accurate diagnosis. The loop-mediated isothermal amplification (LAMP) assay is a promising alternative recommended by the WHO for the initial diagnosis of pulmonary TB, particularly in resource-limited settings. This study evaluated the sensitivity and specificity of a commercial LAMP assay for TB detection using 198 samples from different countries including Mexico. The LAMP assay results were compared to the results of standard tests: AFB smear microscopy, cell culture, and Xpert PCR. Across all samples, LAMP showed a sensitivity of 96.20% and a specificity of 84.61%. When compared specifically to “true positives” and “true negatives” (defined by the consistency across the standard tests), LAMP demonstrated 100% sensitivity and 92.30% specificity. For context, the sensitivity of AFB smear microscopy against the culture and Xpert tests was 79.04%. A significant finding was that the LAMP test detected a high percentage (92.5%) of samples found positive by the culture and Xpert tests but negative by the AFB smear, highlighting its ability to identify cases missed by traditional microscopy. This study concluded that the LAMP assay is a sensitive and specific tool for TB diagnosis with potential for rapid and accurate diagnosis, especially in resource-limited areas. Full article

(This article belongs to the Special Issue Infectious Diseases and Molecular Epidemiology: A Focus on Pathogenic Microorganisms)

21 pages, 810 KiB

Open AccessReview

Molecular Crosstalk and Therapeutic Synergy: Tyrosine Kinase Inhibitors and Cannabidiol in Oral Cancer Treatment

by Zainab Saad Ghafil AlRaheem, Thao T. Le, Ali Seyfoddin and Yan Li

Curr. Issues Mol. Biol. 2025, 47(8), 584; https://doi.org/10.3390/cimb47080584 - 23 Jul 2025

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, with oral squamous cell carcinoma (OSCC) accounting for a significant portion of cases. Despite advancements in treatment, only modest gains have been made in HNSCC/OSCC control. Epidermal growth factor [...] Read more.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, with oral squamous cell carcinoma (OSCC) accounting for a significant portion of cases. Despite advancements in treatment, only modest gains have been made in HNSCC/OSCC control. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have emerged as targeted therapies for OSCC in clinical trials. However, their clinical efficacy remains a challenge. Cannabidiol (CBD), a non-psychoactive phytochemical from cannabis, has demonstrated anticancer and immunomodulatory properties. CBD induces apoptosis and autophagy and modulates signaling pathways often dysregulated in HNSCC. This review summarizes the molecular mechanisms of EGFR-TKIs and CBD and their clinical insights and further discusses potential implications of combination targeted therapies. Full article

(This article belongs to the Special Issue Novel Drugs and Natural Products Discovery)

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34 pages, 800 KiB

Open AccessReview

The Role of miRNAs and Extracellular Vesicles in Adaptation After Resistance Exercise: A Review

by Dávid Csala, Zoltán Ádám and Márta Wilhelm

Curr. Issues Mol. Biol. 2025, 47(8), 583; https://doi.org/10.3390/cimb47080583 - 23 Jul 2025

Resistance exercise can enhance or preserve muscle mass and/or strength. Modifying factors are secreted following resistance exercise. Biomarkers like cytokines and extracellular vesicles, especially small extracellular vesicles, are released into the circulation and play an important role in cell-to-cell and inter-tissue communications. There [...] Read more.

Resistance exercise can enhance or preserve muscle mass and/or strength. Modifying factors are secreted following resistance exercise. Biomarkers like cytokines and extracellular vesicles, especially small extracellular vesicles, are released into the circulation and play an important role in cell-to-cell and inter-tissue communications. There is increasing evidence that physical activity itself promotes the release of extracellular vesicles into the bloodstream, suggesting the importance of vesicles in mediating systemic adaptations following exercise. Extracellular vesicles contain proteins, nucleic acids like miRNAs, and other molecules targeting different cell types and tissues of distant organs. Therefore, extracellular vesicles and encapsulated miRNAs are fine tuners of protein synthesis and are important in the adaptation after resistance training. However, there is a lack of strong data supporting the precise mechanisms of these processes. In this literature review, we collected publications related to miRNA and extracellular vesicle profile changes induced by resistance exercise. To the best of our knowledge, the changes in human extracellular vesicle and microRNA profiles following resistance exercise have not been reviewed yet. We aimed to assess the shortcomings and difficulties characterizing this research area, to summarize the existing results to date, and to propose possible solutions that could help standardize the implementation of future investigations. Full article

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

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16 pages, 2162 KiB

Open AccessReview

Teriparatide for Guided Bone Regeneration in Craniomaxillofacial Defects: A Systematic Review of Preclinical Studies

by Jessika Dethlefs Canto, Carlos Fernando Mourão, Vittorio Moraschini, Rafael da Silva Bonato, Suelen Cristina Sartoretto, Monica Diuana Calasans-Maia, José Mauro Granjeiro and Rafael Seabra Louro

Curr. Issues Mol. Biol. 2025, 47(8), 582; https://doi.org/10.3390/cimb47080582 - 23 Jul 2025

This systematic review aimed to evaluate the effectiveness of teriparatide (TP) in guided bone regeneration (GBR). An electronic search without language or date restrictions was performed in PubMed, Web of Science, Scopus, Scielo, and gray literature for articles published until June 2025. Inclusion [...] Read more.

This systematic review aimed to evaluate the effectiveness of teriparatide (TP) in guided bone regeneration (GBR). An electronic search without language or date restrictions was performed in PubMed, Web of Science, Scopus, Scielo, and gray literature for articles published until June 2025. Inclusion criteria considered studies evaluating the effect of TP on bone regeneration, analyzed using SYRCLE’s Risk of Bias tool. Twenty-four preclinical studies were included, covering diverse craniofacial models (mandibular, calvarial, extraction sockets, sinus augmentation, distraction osteogenesis, segmental defects) and employing systemic or local TP administration. Teriparatide consistently enhanced osteogenesis, graft integration, angiogenesis, and mineralization, with potentiated effects when combined with various biomaterials, including polyethylene glycol (PEG), hydroxyapatite/tricalcium phosphate (HA/TCP), biphasic calcium phosphate (BCP), octacalcium phosphate collagen (OCP/Col), enamel matrix derivatives (EMDs), autografts, allografts, xenografts (Bio-Oss), strontium ranelate, and bioactive glass. Critically, most studies presented a moderate-to-high risk of bias, with insufficient randomization, allocation concealment, and blinding, which limited the internal validity of the findings. TP shows promising osteoanabolic potential in guided bone regeneration, enhancing bone formation, angiogenesis, and scaffold integration across preclinical models. Nonetheless, its translation to clinical practice requires well-designed human randomized controlled trials to define optimal dosing strategies, long-term safety, and its role in oral and craniomaxillofacial surgical applications. Full article

(This article belongs to the Special Issue Osteoclastogenesis and Osteogenesis: Physiological and Molecular Responses to Xenobiotics and Biomaterials)

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Graphical abstract

14 pages, 1664 KiB

Open AccessArticle

Depletion of IGFALS Serum Level up to 3 Months After Cardiac Surgery, with Exploration of Potential Relationships to Surrogates of Organ Failures and Clinical Outcomes

by Krzysztof Laudanski, Mohamed A. Mahmoud, Hossam Gad and Daniel A. Diedrich

Curr. Issues Mol. Biol. 2025, 47(8), 581; https://doi.org/10.3390/cimb47080581 - 23 Jul 2025

The insulin-like growth factor binding protein, acid-labile subunit (IGFALS), plays a crucial role in glucose metabolism and immune regulation, key processes in recovery from surgery. Here, we studied the perioperative serum IGFALS dynamics and explored potential clinical implications. A total of 79 patients [...] Read more.

The insulin-like growth factor binding protein, acid-labile subunit (IGFALS), plays a crucial role in glucose metabolism and immune regulation, key processes in recovery from surgery. Here, we studied the perioperative serum IGFALS dynamics and explored potential clinical implications. A total of 79 patients undergoing elective cardiac surgery with implementation of cardiopulmonary bypass had their serum isolated at baseline, 24 h, seven days, and three months postoperatively to assess serum concentrations of IGFALS and insulin growth factor 1 (IGF-1). Markers of perioperative injury included troponin I (TnI), high-mobility group box 1 (HMGB-1), and heat shock protein 60 (Hsp-60). Inflammatory status was assessed via interleukin-6 (IL-6) and interleukin-8 (IL-8). Additionally, we measured in vitro cytokine production to viral stimulation of whole blood and monocytes. Surrogates of neuronal distress included neurofilament light chain (NF-L), total tau (τ), phosphorylated tau at threonine 181 (τp181), and amyloid β40 and β42. Renal impairment was defined by RIFLE criteria. Cardiac dysfunction was denoted by serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Serum IGFALS levels declined significantly after surgery and remained depressed even at 3 months. Administration of acetaminophen and acetylsalicylic acid differentiated IGFALS levels at the 24 h postoperatively. Serum IGFALS 24 h post-operatively correlated with production of cytokines by leukocytes after in vitro viral stimulation. Serum amyloid-β1-42 was significantly associated with IGFALS at baseline and 24 h post-surgery Patients discharged home had higher IGFALS levels at 28 days and 3 months than those discharged to healthcare facilities or who died. These findings suggest that IGFALS may serve as a prognostic biomarker for recovery trajectory and postoperative outcomes in cardiac surgery patients. Full article

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

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35 pages, 1902 KiB

Open AccessReview

From Amyloid to Synaptic Dysfunction: Biomarker-Driven Insights into Alzheimer’s Disease

by Luisa Agnello, Caterina Maria Gambino, Anna Maria Ciaccio, Francesco Cacciabaudo, Davide Massa, Anna Masucci, Martina Tamburello, Roberta Vassallo, Mauro Midiri, Concetta Scazzone and Marcello Ciaccio

Curr. Issues Mol. Biol. 2025, 47(8), 580; https://doi.org/10.3390/cimb47080580 - 22 Jul 2025

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and represents a major public health challenge. With increasing life expectancy, the incidence of AD has also increased, highlighting the need for early diagnosis and improved monitoring. Traditionally, diagnosis has relied on clinical symptoms [...] Read more.

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and represents a major public health challenge. With increasing life expectancy, the incidence of AD has also increased, highlighting the need for early diagnosis and improved monitoring. Traditionally, diagnosis has relied on clinical symptoms and neuroimaging; however, the introduction of biomarkers has revolutionized disease assessment. Traditional biomarkers, including the Aβ42/Aβ40 ratio, phosphorylated tau (p-Tau181, p-Tau217, and p-Tau231), total tau (t-tau), and neurofilament light chain (NfL), are fundamental for staging AD progression. Updated guidelines introduced the ATX(N) model, which extends biomarker classification to include additional promising biomarkers, such as SNAP-25, YKL-40, GAP-43, VILIP-1, progranulin (PGRN), TREM2, IGF-1, hFABP, MCP-1, TDP-43, and BDNF. Recent advancements have allowed for the detection of these biomarkers not only in CSF but also in plasma and neuron-derived exosomes, offering less invasive and more accessible diagnostic options. This review explores established and emerging biomarkers and emphasizes their roles in early diagnosis, patient stratification, and precision medicine. Full article

(This article belongs to the Section Molecular Medicine)

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13 pages, 4863 KiB

Open AccessArticle

p53 Protein Stability Plays a Crucial Role in NaB-Mediated Apoptosis in Colorectal Cancer Cells

by Jeong Yeon Lee and Hyunju Kim

Curr. Issues Mol. Biol. 2025, 47(8), 579; https://doi.org/10.3390/cimb47080579 - 22 Jul 2025

Colorectal cancer (CRC) is associated with factors such as an unhealthy diet, physical inactivity, obesity, diabetes, and chronic inflammatory conditions like inflammatory bowel disease (IBD), as well as TP53 mutations, which are observed in a broad spectrum of CRC. Additionally, alteration in the [...] Read more.

Colorectal cancer (CRC) is associated with factors such as an unhealthy diet, physical inactivity, obesity, diabetes, and chronic inflammatory conditions like inflammatory bowel disease (IBD), as well as TP53 mutations, which are observed in a broad spectrum of CRC. Additionally, alteration in the composition of the gut microbiome community and metabolism plays a significant role in the development of colorectal cancer and its therapeutic effects. It is well known that treatment with sodium butyrate (NaB), an intestinal microbial metabolite, can induce apoptosis by activating histone deacetylase (HDAC) in cancer cells. Therefore, this study examined the relationship between NaB-induced apoptosis and p53 protein level in colorectal cancer cells. Treatment with NaB triggered cell death in the HCT116 cell line. Furthermore, a notable elevation in p53 protein level was detected following treatment with a high concentration of NaB, compared to both the control group and the low concentration NaB. Furthermore, apoptotic cell death was diminished in a p53-deficient cell line (HCT 116 p53^−/−) and p53 protein expression was more stabilized. Although p53 mRNA expression was not affected, acetylation of p53 protein was clearly observed by high concentration NaB treatment. To demonstrate the relationship between p53 acetylation and cell death, HT29 cells were treated with a high concentration of NaB. In HT29 cells with a mutation in the p53 gene, increased cell viability, overproduction p53 protein, and hyperacetylation of p53 were observed compared to the control. The results of this study suggest that p53 protein expression plays an important role in the effectiveness of therapy utilizing gut microbiota metabolites. Full article

(This article belongs to the Section Molecular Medicine)

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3 pages, 150 KiB

Open AccessEditorial

Editorial for the Special Issue “Advances in Molecular Biology Methods in Hepatology Research”

by Dileep G. Nair and Ralf Weiskirchen

Curr. Issues Mol. Biol. 2025, 47(8), 578; https://doi.org/10.3390/cimb47080578 - 22 Jul 2025

We are delighted to present this Special Issue of Current Issues in Molecular Biology, entitled “Advances in Molecular Biology Methods in Hepatology Research [...] Full article

(This article belongs to the Special Issue Advances in Molecular Biology Methods in Hepatology Research)

29 pages, 2729 KiB

Open AccessArticle

Computational Evaluation and Multi-Criteria Optimization of Natural Compound Analogs Targeting SARS-CoV-2 Proteases

by Paul Andrei Negru, Andrei-Flavius Radu, Ada Radu, Delia Mirela Tit and Gabriela Bungau

Curr. Issues Mol. Biol. 2025, 47(7), 577; https://doi.org/10.3390/cimb47070577 - 21 Jul 2025

The global impact of the COVID-19 crisis has underscored the need for novel therapeutic candidates capable of efficiently targeting essential viral proteins. Existing therapeutic strategies continue to encounter limitations such as reduced efficacy against emerging variants, safety concerns, and suboptimal pharmacodynamics, which emphasize [...] Read more.

The global impact of the COVID-19 crisis has underscored the need for novel therapeutic candidates capable of efficiently targeting essential viral proteins. Existing therapeutic strategies continue to encounter limitations such as reduced efficacy against emerging variants, safety concerns, and suboptimal pharmacodynamics, which emphasize the potential of natural-origin compounds as supportive agents with immunomodulatory, anti-inflammatory, and antioxidant benefits. The present study significantly advances prior molecular docking research through comprehensive virtual screening of structurally related analogs derived from antiviral phytochemicals. These compounds were evaluated specifically against the SARS-CoV-2 main protease (3CLpro) and papain-like protease (PLpro). Utilizing chemical similarity algorithms via the ChEMBL database, over 600 candidate molecules were retrieved and subjected to automated docking, interaction pattern analysis, and comprehensive ADMET profiling. Several analogs showed enhanced binding scores relative to their parent scaffolds, with CHEMBL1720210 (a shogaol-derived analog) demonstrating strong interaction with PLpro (−9.34 kcal/mol), and CHEMBL1495225 (a 6-gingerol derivative) showing high affinity for 3CLpro (−8.04 kcal/mol). Molecular interaction analysis revealed that CHEMBL1720210 forms hydrogen bonds with key PLpro residues including GLY163, LEU162, GLN269, TYR265, and TYR273, complemented by hydrophobic interactions with TYR268 and PRO248. CHEMBL1495225 establishes multiple hydrogen bonds with the 3CLpro residues ASP197, ARG131, TYR239, LEU272, and GLY195, along with hydrophobic contacts with LEU287. Gene expression predictions via DIGEP-Pred indicated that the top-ranked compounds could influence biological pathways linked to inflammation and oxidative stress, processes implicated in COVID-19’s pathology. Notably, CHEMBL4069090 emerged as a lead compound with favorable drug-likeness and predicted binding to PLpro. Overall, the applied in silico framework facilitated the rational prioritization of bioactive analogs with promising pharmacological profiles, supporting their advancement toward experimental validation and therapeutic exploration against SARS-CoV-2. Full article

(This article belongs to the Special Issue Novel Drugs and Natural Products Discovery)

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16 pages, 3669 KiB

Open AccessArticle

Functional Analysis of Malus halliana WRKY69 Transcription Factor (TF) Under Iron (Fe) Deficiency Stress

by Hongjia Luo, Wenqing Liu, Xiaoya Wang and Yanxiu Wang

Curr. Issues Mol. Biol. 2025, 47(7), 576; https://doi.org/10.3390/cimb47070576 - 21 Jul 2025

Fe deficiency in apple trees can lead to leaf chlorosis and impede root development, resulting in significant alterations in signaling, metabolism, and genetic functions, which severely restricts fruit yield and quality. It is well established that WRKY transcription factors (TFs) are of vital [...] Read more.

Fe deficiency in apple trees can lead to leaf chlorosis and impede root development, resulting in significant alterations in signaling, metabolism, and genetic functions, which severely restricts fruit yield and quality. It is well established that WRKY transcription factors (TFs) are of vital significance in mediating plant responses to abiotic stress. Real-time quantitative fluorescence (RT-qPCR) analysis displayed that Fe deficiency stress can significantly induce WRKY69 TF gene expression. However, the potential mechanisms by which the WRKY69 gene involved in Fe deficiency stress remains to be investigated. To address this limitations, the WRKY69 gene (MD09G1235100) was successfully isolated from apple rootstock Malus halliana and performed both homologous and heterologous expression analyses in apple calli and tobacco to elucidate its functional role in response to Fe deficiency stress. The findings indicated that transgenic tobacco plants exhibited enhanced growth vigor and reduced chlorosis when subjected to Fe deficiency stress compared to the wild type (WT). Additionally, the apple calli that were overexpressed WRKY69 also exhibited superior growth and quality. Furthermore, the overexpression of the WRKY69 gene enhanced the ability of tobacco to Fe deficiency stress tolerance by stimulating the synthesis of photosynthetic pigments, increasing antioxidant enzyme activity, and facilitating Fe reduction. Additionally, it increased the resistance of apple calli to Fe deficiency stress by enhancing Fe reduction and elevating the activity of antioxidant enzymes. For example, under Fe deficiency stress, the proline (Pro) contents of the overexpression lines (OE-2, OE-5, OE-6) were 26.18 mg·g⁻¹, 26.13 mg·g⁻¹, and 26.27 mg·g⁻¹, respectively, which were 16.98%, 16.76%, and 17.38% higher than the proline content of 22.38 mg·g⁻¹ in the wild-type lines, respectively. To summarize, a functional analysis of tobacco plants and apple calli displayed that WRKY69 TF serves as a positive regulator under Fe deficiency stress, which provides candidate genetic resources for cultivating apple rootstocks or varieties with strong stress (Fe deficiency) resistance. Full article

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

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17 pages, 646 KiB

Open AccessArticle

Screening of Potential Drug Targets Based on the Genome-Scale Metabolic Network Model of Vibrio parahaemolyticus

by Lingrui Zhang, Bin Wang, Ruiqi Zhang, Zhen He, Mingzhi Zhang, Tong Hao and Jinsheng Sun

Curr. Issues Mol. Biol. 2025, 47(7), 575; https://doi.org/10.3390/cimb47070575 - 21 Jul 2025

Vibrio parahaemolyticus is a pathogenic bacterium widely distributed in marine environments, posing significant threats to aquatic organisms and human health. The overuse and misuse of antibiotics has led to the development of multidrug- and pan-resistant V. parahaemolyticus strains. There is an urgent need [...] Read more.

Vibrio parahaemolyticus is a pathogenic bacterium widely distributed in marine environments, posing significant threats to aquatic organisms and human health. The overuse and misuse of antibiotics has led to the development of multidrug- and pan-resistant V. parahaemolyticus strains. There is an urgent need for novel antibacterial therapies with innovative mechanisms of action. In this work, a genome-scale metabolic network model (GMSN) of V. parahaemolyticus, named VPA2061, was reconstructed to predict the metabolites that can be explored as potential drug targets for eliminating V. parahaemolyticus infections. The model comprises 2061 reactions and 1812 metabolites. Through essential metabolite analysis and pathogen–host association screening with VPA2061, 10 essential metabolites critical for the survival of V. parahaemolyticus were identified, which may serve as key candidates for developing new antimicrobial strategies. Additionally, 39 structural analogs were found for these essential metabolites. The molecular docking analysis of the essential metabolites and structural analogs further investigated the potential value of these metabolites for drug design. The GSMN reconstructed in this work provides a new tool for understanding the pathogenic mechanisms of V. parahaemolyticus. Furthermore, the analysis results regarding the essential metabolites hold profound implications for the development of novel antibacterial therapies for V. parahaemolyticus-related disease. Full article

(This article belongs to the Section Molecular Microbiology)

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11 pages, 231 KiB

Open AccessArticle

Tempol Induces Oxidative Stress, ER Stress and Apoptosis via MAPK/Akt/mTOR Pathway Suppression in HT29 (Colon) and CRL-1739 (Gastric) Cancer Cell Lines

by Gorkem Ozdemir and Halil Mahir Kaplan

Curr. Issues Mol. Biol. 2025, 47(7), 574; https://doi.org/10.3390/cimb47070574 - 21 Jul 2025

Tempol is a synthetic antioxidant that shows promise in preclinical cancer studies by inhibiting growth and inducing apoptosis. Given that the Mitogen-Activated Protein Kinase (MAPK) and Protein Kinase B/Mammalian Target of Rapamycin (Akt/mTOR) signaling pathways are frequently dysregulated in gastric and colon cancers [...] Read more.

Tempol is a synthetic antioxidant that shows promise in preclinical cancer studies by inhibiting growth and inducing apoptosis. Given that the Mitogen-Activated Protein Kinase (MAPK) and Protein Kinase B/Mammalian Target of Rapamycin (Akt/mTOR) signaling pathways are frequently dysregulated in gastric and colon cancers and contribute to their progression, we investigated Tempol’s anti-cancer potential in HT29 (colon) and CRL-1739 (gastric) cancer cells. Cells were treated with 2 mM Tempol for 48 h, with untreated cells as controls. We evaluated apoptosis (Bax, cleaved caspase-3, and Bcl-2), key signaling pathway activity (p-ERK, p-JNK, p-AKT, and p-mTOR), and levels of stress- and apoptosis-related proteins (WEE1, GADD153, GRP78, and AIF). Tempol significantly increased pro-apoptotic Bax and cleaved caspase-3 (p < 0.0001) and decreased anti-apoptotic Bcl-2 (p < 0.0001) in both cell lines. Furthermore, Tempol markedly reduced the activity of p-ERK, p-JNK, p-AKT, and p-mTOR (p < 0.0001) and significantly increased the protein levels of WEE1, GADD153, GRP78, and AIF (p < 0.0001). Tempol treatment also led to a significant increase in total oxidant status and a decrease in total antioxidant status. In conclusion, our findings suggest that Tempol exhibits its anti-cancer activity through multiple interconnected mechanisms, primarily inducing apoptosis and oxidative stress, while concurrently suppressing pro-survival signaling pathways. These results highlight Tempol’s potential as a therapeutic agent for gastric and colon cancers. Full article

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

17 pages, 3958 KiB

Open AccessArticle

ZmNLR-7-Mediated Synergistic Regulation of ROS, Hormonal Signaling, and Defense Gene Networks Drives Maize Immunity to Southern Corn Leaf Blight

by Bo Su, Xiaolan Yang, Rui Zhang, Shijie Dong, Ying Liu, Hubiao Jiang, Guichun Wu and Ting Ding

Curr. Issues Mol. Biol. 2025, 47(7), 573; https://doi.org/10.3390/cimb47070573 - 21 Jul 2025

The rapid evolution of pathogens and the limited genetic diversity of hosts are two major factors contributing to the plant pathogenic phenomenon known as the loss of disease resistance in maize (Zea mays L.). It has emerged as a significant biological stressor [...] Read more.

The rapid evolution of pathogens and the limited genetic diversity of hosts are two major factors contributing to the plant pathogenic phenomenon known as the loss of disease resistance in maize (Zea mays L.). It has emerged as a significant biological stressor threatening the global food supplies and security. Based on previous cross-species homologous gene screening assays conducted in the laboratory, this study identified the maize disease-resistance candidate gene ZmNLR-7 to investigate the maize immune regulation mechanism against Bipolaris maydis. Subcellular localization assays confirmed that the ZmNLR-7 protein is localized in the plasma membrane and nucleus, and phylogenetic analysis revealed that it contains a conserved NB-ARC domain. Analysis of tissue expression patterns revealed that ZmNLR-7 was expressed in all maize tissues, with the highest expression level (5.11 times) exhibited in the leaves, and that its transcription level peaked at 11.92 times 48 h post Bipolaris maydis infection. Upon inoculating the ZmNLR-7 EMS mutants with Bipolaris maydis, the disease index was increased to 33.89 and 43.33, respectively, and the lesion expansion rate was higher than that in the wild type, indicating enhanced susceptibility to southern corn leaf blight. Physiological index measurements revealed a disturbance of ROS metabolism in ZmNLR-7 EMS mutants, with SOD activity decreased by approximately 30% and 55%, and POD activity decreased by 18% and 22%. Moreover, H₂O₂ content decreased, while lipid peroxide MDA accumulation increased. Transcriptomic analysis revealed a significant inhibition of the expression of the key genes NPR1 and ACS6 in the SA/ET signaling pathway and a decrease in the expression of disease-related genes ERF1 and PR1. This study established a new paradigm for the study of NLR protein-mediated plant immune mechanisms and provided target genes for molecular breeding of disease resistance in maize. Overall, these findings provide the first evidence that ZmNLR-7 confers resistance to southern corn leaf blight in maize by synergistically regulating ROS homeostasis, SA/ET signal transduction, and downstream defense gene expression networks. Full article

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

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18 pages, 1491 KiB

Open AccessReview

Effects of Aerobic Exercise on Sleep Quality, Insomnia, and Inflammatory Markers: A Systematic Review and Meta-Analysis

by Mariazel Rubio-Valles and Arnulfo Ramos-Jimenez

Curr. Issues Mol. Biol. 2025, 47(7), 572; https://doi.org/10.3390/cimb47070572 - 20 Jul 2025

Poor sleep quality and insomnia are increasingly linked to chronic inflammation and obesity-related metabolic dysfunction. Aerobic exercise is a promising non-pharmacological approach for enhancing sleep quality and reducing systemic inflammation; Therefore, we aim to systematically evaluate and quantify the effects of aerobic exercise [...] Read more.

Poor sleep quality and insomnia are increasingly linked to chronic inflammation and obesity-related metabolic dysfunction. Aerobic exercise is a promising non-pharmacological approach for enhancing sleep quality and reducing systemic inflammation; Therefore, we aim to systematically evaluate and quantify the effects of aerobic exercise interventions on subjective sleep quality, insomnia severity, and circulating markers (IL-6 and TNF-α) in adults. A systematic search was conducted in institutional databases (UNAM, UACJ) and PubMed to identify randomized controlled trials (RCTs) examining the effects of exercise on sleep and inflammation. Risk of bias was assessed using the Cochrane RoB2 tool. Meta-analyses were performed using RevMan 5.4 with random-effects models to estimate pooled mean differences (MD) and standardized mean differences (SMD), with 95% confidence intervals. Anaerobic protocols were excluded from the meta-analysis due to the insufficient availability of data. : Eleven RCTs met the inclusion criteria. Aerobic exercise showed a significant pooled effect on sleep outcomes (MD = −2.51; 95% CI: −4.80 to −0.23; p = 0.03). However, subgroup analyses for Pittsburgh Sleep Quality Index (PSQI) (MD = −2.27; p = 0.15) and Insomnia Severity Index (ISI) (MD = −2.98; p = 0.16) were not statistically significant. Two studies on IL-6 reported a non-significant reduction (SMD = −0.17; p = 0.66), with moderate heterogeneity. TNF-α results were also non-significant (SMD = 0.60; p = 0.29) with substantial variability. Our results showed that aerobic exercise may modestly improve sleep outcomes; however, current evidence does not support its effectiveness in reducing levels of IL-6 or TNF-α. Further well-controlled trials are needed to clarify its immunometabolic effects, particularly in populations with obesity or metabolic disorders. Full article

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

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22 pages, 1438 KiB

Open AccessArticle

The Transcription Machinery and the Driving Force of the Transcriptional Molecular Condensate: The Role of Phosphates

by Raúl Riera Aroche, Esli C. Sánchez Moreno, Yveth M. Ortiz García, Andrea C. Machado Sulbarán, Lizbeth Riera Leal, Luis R. Olivas Román and Annie Riera Leal

Curr. Issues Mol. Biol. 2025, 47(7), 571; https://doi.org/10.3390/cimb47070571 - 20 Jul 2025

The dynamic phosphorylation of the human RNA Pol II CTD establishes a code applicable to all eukaryotic transcription processes. However, the ability of these specific post-translational modifications to convey molecular signals through structural changes remains unclear. We previously explained that each gene can [...] Read more.

The dynamic phosphorylation of the human RNA Pol II CTD establishes a code applicable to all eukaryotic transcription processes. However, the ability of these specific post-translational modifications to convey molecular signals through structural changes remains unclear. We previously explained that each gene can be modeled as a combination of n circuits connected in parallel. RNA Pol II accesses these circuits and, through a series of pulses, matches the resonance frequency of the DNA qubits, enabling it to extract genetic information and quantum teleport it. Negatively charged phosphates react under RNA Pol II catalysis, which increases the electron density on the deoxyribose acceptor carbon (2’C in the DNA sugar backbone). The phosphorylation effect on the stability of a carbon radical connects tyrosine to the nitrogenous base, while the subsequent pulses link the protein to molecular water through hydrogen bonds. The selective activation of inert C(sp³)–H bonds begins by reading the quantum information stored in the nitrogenous bases. The coupling of hydrogen proton transfer with electron transfer in water generates a supercurrent, which is explained by the correlation of pairs of the same type of fermions exchanging a boson. All these changes lead to the formation of a molecular protein–DNA–water transcriptional condensate. Full article

(This article belongs to the Special Issue Post-Translational Modification Networks in Disease and Therapy: From Chromatin Regulation to Protein Stability)

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16 pages, 1464 KiB

Open AccessArticle

Yeast Oral Delivery of DAF16 shRNAs Results in Effective Gene Silencing in C. elegans

by Benedetta Caraba, Arianna Montanari, Emily Schifano, Fabiana Stocchi, Giovanna Costanzo, Daniela Uccelletti and Cristina Mazzoni

Curr. Issues Mol. Biol. 2025, 47(7), 570; https://doi.org/10.3390/cimb47070570 - 20 Jul 2025

Plant Parasitic Nematodes (PPNs) are a major problem in agriculture. Damage caused by PPNs has been estimated at USD 80–157 billion annually. The estimates could be even worse in the future in the context of a growing world population in a climate change [...] Read more.

Plant Parasitic Nematodes (PPNs) are a major problem in agriculture. Damage caused by PPNs has been estimated at USD 80–157 billion annually. The estimates could be even worse in the future in the context of a growing world population in a climate change scenario and with the removal/reduction in the use of some nematodicides due to the strong ecological impact. Biocontrol Agents (BCAs) currently constitute only 8.8% of the general pesticide market. With a view to an ecological transition, the transition from pesticides to biopesticides represents an important challenge that appears necessary not only for organic farming, but also in so-called integrated agriculture. Among the possible BCAs, microorganisms, and in particular yeast, which enjoys the GRAS (Generally Recognized As Safe) status, have the advantage of being able to be produced on a large scale by fermentation on waste substrates at low cost. In this paper, as proof of concept we constructed yeast strains expressing short hairpin RNAs (shRNAs) targeting the daf-16 gene in C. elegans. We demonstrate that oral ingestion of yeast cells expressing DAF16 shRNA is efficient in lowering daf-16 expression and lifespan, suggesting a sustainable RNA interference-based strategy to inhibit the development of PPNs. Full article

(This article belongs to the Collection Feature Papers in Current Issues in Molecular Biology)

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