Current Issues in Molecular Biology

17 pages, 4874 KiB

Open AccessArticle

Detection of Helicobacter pylori and the Genotypes of Resistance to Clarithromycin, Fluoroquinolones, and Metronidazole in Gastric Biopsies: An In Silico Analysis to Help Understand Antibiotic Resistance

by Pedro Valada, Ana Mata, Rui M. M. Brito, Teresa Gonçalves, José A. Medeiros and Célia Nogueira

Curr. Issues Mol. Biol. 2025, 47(3), 187; https://doi.org/10.3390/cimb47030187 - 13 Mar 2025

Abstract

Antibiotic resistance in Helicobacter pylori is increasing rapidly and emerging as a major factor in treatment failure. We aimed to identify genetic mutations associated with resistance to clarithromycin (23S rRNA peptidyl transferase), fluoroquinolones (gyrA), and metronidazole (rdxA), and to [...] Read more.

Antibiotic resistance in Helicobacter pylori is increasing rapidly and emerging as a major factor in treatment failure. We aimed to identify genetic mutations associated with resistance to clarithromycin (23S rRNA peptidyl transferase), fluoroquinolones (gyrA), and metronidazole (rdxA), and to explore their mechanisms of action through molecular modeling. H. pylori detection and the molecular characterization of genes were conducted directly on gastric biopsies by real-time PCR followed by nucleotide sequencing. A 3D model was used to evaluate molecular interactions between the antibiotics and respective target proteins. H. pylori was identified in 66.7% of 33 patients. An analysis of 23SrRNA revealed novel mutations that, by in silico analysis, do not appear to contribute to clarithromycin resistance. In gyrA, mutations in amino acid residues 87 and 91 had an incidence of 27%, and the in silico analysis revealed that these positions are relevant in the binding and resistance to fluoroquinolones. It is also reported for other mutations, some of which are never described. All rdxA mutations were missense, with R16H, M56V, H97T, G98S, A118T, V123T, and R131K predicted by in silico analysis to impact metronidazole resistance. Monitoring H. pylori gene mutations is crucial for tailoring effective antibiotic therapies. Our study advances personalized medicine by introducing novel methods to detect resistance-related mutations and uncovering the molecular mechanisms driving this resistance. Full article

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

► Show Figures

Figure 1

13 pages, 1944 KiB

Open AccessArticle

Antioxidant Mechanisms of the Protective Action of Selenase in Experimental Chronic Generalized Periodontitis

by Valeriy Salnykov, Igor Belenichev, Lyudmyla Makyeyeva, Dmytro Skoryna, Valentyn Oksenych and Oleksandr Kamyshnyi

Curr. Issues Mol. Biol. 2025, 47(3), 186; https://doi.org/10.3390/cimb47030186 - 12 Mar 2025

Abstract

Inflammatory periodontal diseases, despite all the efforts of modern dentistry, remain an important predictor of tooth loss worldwide. Oxidative stress plays a crucial role in the pathogenesis of periodontitis, making the use of antioxidants an attractive option for its treatment. Our attention was [...] Read more.

Inflammatory periodontal diseases, despite all the efforts of modern dentistry, remain an important predictor of tooth loss worldwide. Oxidative stress plays a crucial role in the pathogenesis of periodontitis, making the use of antioxidants an attractive option for its treatment. Our attention was drawn to the selenium compound Selenase as an antioxidant therapeutic agent. In this study, we modeled a calcium-deficient prooxidant chronic generalized periodontitis (CGP) model in white non-linear rats. Then, after 14 days, Selenase (50 μg/kg) and Mexidol (250 mg/kg) were administered intragastrically. Blood samples from the animals were analyzed using ELISA and biochemical methods to determine Cu-Zn SOD, nitrotyrosine, GPX-4, iNOS, NO_x, GSH, and GSSG levels. The CGP model led to the typical clinical signs of periodontitis, including hyperemia, edema, gingival pocket formation, bleeding, tooth mobility, as well as an increase in molecular–biochemical markers of nitrosative stress and a reduction of endogenous antioxidants in the blood. Selenase resulted in a decrease in the clinical manifestations of CGP, reduced iNOS, nitrotyrosine, and NO_x levels, and an increase in Cu-Zn SOD and GPX-4 compared to the control group (p < 0.05). Mexidol had a less pronounced effect on these markers compared to Selenase (p < 0.05). Full article

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

► Show Figures

Figure 1

19 pages, 2966 KiB

Open AccessArticle

Anti-Infective Screening of Selected Nine Cannabinoids Against Clostridium perfringens and Influenza A (H5N1) Neuraminidases, and SARS-CoV-2 Main Protease and Spike Protein Interactions

by Thanet Pitakbut and Oliver Kayser

Curr. Issues Mol. Biol. 2025, 47(3), 185; https://doi.org/10.3390/cimb47030185 - 12 Mar 2025

Abstract

Recently, cannabinoids have gained scientific interest as a promising anti-infective natural product class, as reported in several studies. However, the existing knowledge is mainly limited to common cannabinoids like THC and CBD. Therefore, this study aims to fill the knowledge gap by investigating [...] Read more.

Recently, cannabinoids have gained scientific interest as a promising anti-infective natural product class, as reported in several studies. However, the existing knowledge is mainly limited to common cannabinoids like THC and CBD. Therefore, this study aims to fill the knowledge gap by investigating the anti-infective potential of nine selected cannabinoids (both common and rare cannabinoids): THC, CBD, CBC, CBE, CBF, CBG, CBL, CBN, and CBT against Clostridium perfringens and Influenza A (H5N1) neuraminidases and SARS-CoV-2 main protease and spike protein–human ACE2 interaction using a standard in vitro biochemical enzyme-binding assay. As a result, to the authors’ knowledge, this study is the first to demonstrate the most promising effect of CBG over others in its class against C. perfringens and influenza A (H5N1) neuraminidases and SARS-CoV-2 main protease and spike protein–human ACE2 interaction. In comparison to CBG, CBD and THC were the second and third most promising candidates. Meanwhile, the other derivatives, such as CBC, CBE, CBF, CBL, CBN, and CBT, showed at least one anti-infective effect. Our findings during the early drug discovery process indicate a promising anti-infective potential of cannabinoids, which can be considered for further investigation in a biological setup. Full article

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

► Show Figures

Figure 1

14 pages, 274 KiB

Open AccessArticle

A Comparison of the Treatment Effects of a Risperidone Solution, an Equal Ratio of DHA/ARA, and a Larger Ratio of Omega-6 PUFA Added to Omega-3 PUFA: An Open-Label Clinical Trial

by Kunio Yui and George Imataka

Curr. Issues Mol. Biol. 2025, 47(3), 184; https://doi.org/10.3390/cimb47030184 - 12 Mar 2025

Abstract

We aimed to assess the efficacy, safety, and pharmacokinetics of an oral risperidone solution and two types of supplementations with PUFAs. We assigned 39 participants with mild ASD (mean age ± standard deviation = 14.6 ± 6.0 years) to three treatment groups (each [...] Read more.

We aimed to assess the efficacy, safety, and pharmacokinetics of an oral risperidone solution and two types of supplementations with PUFAs. We assigned 39 participants with mild ASD (mean age ± standard deviation = 14.6 ± 6.0 years) to three treatment groups (each n = 13): RIS-OS; equal doses of 240 mg of omega-3 PUFA docosahexaenoic acid and omega-6 PUFA arachidonic acid (1:1) (aravita); and omega-6 precursor linoleic acid (480 mg) and omega-3 precursor alpha-linolenic acid (120 mg) (4:1) (awake). The primary outcome was the Autism Diagnostic Interview—Revised score. The secondary outcomes were the Social Responsiveness Scale (SRS) and Aberrant Behavior Check scores. The results of the linear mixed-effects model revealed that the RIS-OS group exhibited significant improvement in the SRS subscale scores of social motivation at weeks 8, 12, and 16 compared with the aravita and awake groups, as well as in the SRS subscale score of social mannerisms at weeks 12 and 16 compared with the aravita group. Moreover, the RIS-OS group showed a trend towards significantly lower plasma ceruloplasmin (Cp) levels. Their plasma insulin-like growth factor (IGF) levels were significantly higher at week 8 than in the subsequent weeks. The high Cp and IGF levels may be attributed to reduced neuroinflammation. These findings demonstrate, firstly, that reduced inflammation through increased anti-inflammatory proteins such as Cp and IGF has clinical effects on the motivation–reward system and mannerisms in patients with ASD through the amelioration of dopamine D2, 5-HT2a, and 5-HT2b dysfunction. Full article

(This article belongs to the Special Issue Mental Disorder: Focus on Pathogenesis to Treatment)

2 pages, 177 KiB

Open AccessEditorial

Editorial of Special Issue “Latest Multifactorial Developments on Neuropsychiatric Disorders and Manifestations”

by Cătălina Ionescu and Alin Ciobica

Curr. Issues Mol. Biol. 2025, 47(3), 183; https://doi.org/10.3390/cimb47030183 - 12 Mar 2025

Abstract

This Special Issue, entitled “Latest Multifactorial Developments on Neuropsychiatric Disorders and Manifestations”, underscores the multifactorial nature of neuropsychiatric disorders, highlighting the complex interplay between genetic, molecular, and environmental factors [...] Full article

(This article belongs to the Special Issue Latest Multifactorial Developments on Neuropsychiatric Disorders and Manifestations)

23 pages, 2906 KiB

Open AccessArticle

The Legacy of COVID-19 in Breast Milk: The Association of Elevated Anti-Inflammatory and Antimicrobial Proteins with Vaccination or Infection

by Felicia Trofin, Petru Cianga, Daniela Constantinescu, Luminița Smaranda Iancu, Roxana Irina Iancu, Diana Păduraru, Eduard Vasile Nastase, Elena Roxana Buzilă, Cătălina Luncă, Corina Maria Cianga and Olivia Simona Dorneanu

Curr. Issues Mol. Biol. 2025, 47(3), 182; https://doi.org/10.3390/cimb47030182 - 11 Mar 2025

Abstract

Background: Breast milk is a rich source of antimicrobial and anti-inflammatory compounds, owing to its diverse array of bioactive molecules. This study explores the presence and activity of natural antimicrobial agents in breast milk, particularly in the context of the SARS-CoV-2 pandemic. Materials [...] Read more.

Background: Breast milk is a rich source of antimicrobial and anti-inflammatory compounds, owing to its diverse array of bioactive molecules. This study explores the presence and activity of natural antimicrobial agents in breast milk, particularly in the context of the SARS-CoV-2 pandemic. Materials and Methods: Breast milk samples were collected from 50 breastfeeding mothers, including those who had either been vaccinated against SARS-CoV-2 or had recovered from the infection. These samples were compared with a control group consisting of 10 unvaccinated mothers with no history of COVID-19. Key antimicrobial and immune-regulatory proteins—lactoferrin, lactadherin, furin, tenascin C, granzyme B, and chitinase 3-like 1—were quantified using the Luminex multiplex analyzer. Results and Discussion: All targeted biomarkers were detected in breast milk, providing insights into the immune profile transferred to infants following COVID-19 infection or vaccination. These bioactive molecules highlight breastfeeding’s role in providing passive immunity and antimicrobial protection. The protein levels were found to be influenced by factors such as maternal inflammation, infant age, delivery mode, and parity, emphasizing the dynamic interaction between maternal immunity, lactation biology, and infant development. Conclusion: Breastfeeding serves as a powerful anti-SARS-CoV-2 defense mechanism, supported by the activity of lactoferrin, lactadherin, and furin, reinforcing its critical role in child health. Full article

(This article belongs to the Special Issue The Role of Bioactives in Inflammation)

► Show Figures

Figure 1

36 pages, 2809 KiB

Open AccessReview

The Therapeutic Potential of Baicalin and Baicalein in Breast Cancer: A Systematic Review of Mechanisms and Efficacy

by Bartłomiej Zieniuk and Şuheda Uğur

Curr. Issues Mol. Biol. 2025, 47(3), 181; https://doi.org/10.3390/cimb47030181 - 11 Mar 2025

Abstract

Cancer remains a leading cause of death globally, with breast cancer being the most commonly diagnosed cancer in women. This systematic review focuses on the therapeutic potential of baicalin and baicalein, two bioactive flavonoids derived from Scutellaria baicalensis, in breast cancer treatment. [...] Read more.

Cancer remains a leading cause of death globally, with breast cancer being the most commonly diagnosed cancer in women. This systematic review focuses on the therapeutic potential of baicalin and baicalein, two bioactive flavonoids derived from Scutellaria baicalensis, in breast cancer treatment. These compounds exhibit anticancer properties through mechanisms such as apoptosis induction, cell cycle arrest, and inhibition of metastasis. Baicalin and baicalein modulate key signaling pathways, including NF-κB, PI3K/AKT/mTOR, and Wnt/β-catenin, and have shown efficacy in both in vitro and in vivo models. Their synergy with chemotherapy agents and incorporation into nanotechnology-based delivery systems highlight opportunities to enhance therapeutic outcomes. However, current evidence is predominantly preclinical, with limited clinical trials to validate their safety and efficacy in humans. Challenges such as poor bioavailability and rapid metabolism also underscore the need for advanced formulation strategies. This review synthesizes current evidence on the molecular mechanisms, therapeutic efficacy, and potential applications of baicalin and baicalein in breast cancer research. Full article

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

► Show Figures

Figure 1

15 pages, 21172 KiB

Open AccessArticle

Antineoplastic Activity of Methyl rosmarinate in Glioblastoma Cells

by Maria Vasiliki Benekou, Panagiota Tzitiridou, Theodora Papagrigoriou, Vasiliki Galani, Chrissa Sioka, Athanassios P. Kyritsis, Diamanto Lazari and George A. Alexiou

Curr. Issues Mol. Biol. 2025, 47(3), 180; https://doi.org/10.3390/cimb47030180 - 10 Mar 2025

Abstract

Glioblastoma (GMB) is a remarkably aggressive brain malignancy characterized by high mortality rates, despite continuous advances in therapeutic approaches. Compounds derived from plants are being studied for their potent medicinal properties in the quest for more efficient therapies. This study investigated the anti-glioma [...] Read more.

Glioblastoma (GMB) is a remarkably aggressive brain malignancy characterized by high mortality rates, despite continuous advances in therapeutic approaches. Compounds derived from plants are being studied for their potent medicinal properties in the quest for more efficient therapies. This study investigated the anti-glioma properties of Methyl rosmarinate, a hydroxycinnamic acid isolated from Thymus thracicus Velen, which has previously demonstrated anti-cancer activity in various cell lines. Human glioblastoma cell lines U87 and T98 were treated with Methyl rosmarinate to assess its effect on cell viability, cell cycle distribution and migratory capacity using Trypan blue assay, flow cytometry and scratch wound healing assay, respectively. The combinatorial effects of Methyl rosmarinate and temozolomide were also analyzed with CompoSyn software. According to the outcomes, Methyl rosmarinate significantly reduced cell viability, induced cell death by interfering in cell cycle checkpoints, and inhibited migration in both GMB cell lines. Notably, in U87 cells, the compound showed a synergistic impact with temozolomide, whereas in T98 cells, there was an antagonistic relationship. These results suggest that Methyl rosmarinate has potential anti-glioma properties; however, more in vivo research is needed. Full article

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

► Show Figures

Figure 1

19 pages, 954 KiB

Open AccessReview

Vascular Endothelial Growth Factor Receptors in the Vascularization of Pancreatic Tumors: Implications for Prognosis and Therapy

by Craig Grobbelaar, Vanessa Steenkamp and Peace Mabeta

Curr. Issues Mol. Biol. 2025, 47(3), 179; https://doi.org/10.3390/cimb47030179 - 10 Mar 2025

Abstract

In pancreatic cancer (PC), vascular endothelial growth factor (VEGF) and its primary receptor, vascular endothelial growth factor receptor (VEGFR)-2, are central drivers of angiogenesis and metastasis, with their overexpression strongly associated with poor prognosis. In some PC patients, VEGF levels correlate with disease [...] Read more.

In pancreatic cancer (PC), vascular endothelial growth factor (VEGF) and its primary receptor, vascular endothelial growth factor receptor (VEGFR)-2, are central drivers of angiogenesis and metastasis, with their overexpression strongly associated with poor prognosis. In some PC patients, VEGF levels correlate with disease stage, tumor burden, and survival outcomes. However, therapies targeting VEGF and VEGFR-2, including tyrosine kinase inhibitors (TKIs) and monoclonal antibodies, have demonstrated limited efficacy, partly due to the emergence of resistance mechanisms. Resistance appears to stem from the activation of alternative vascularization pathways. This review explores the multifaceted roles of VEGFRs in pancreatic cancer, including VEGFR-1 and VEGFR-3. Potential strategies to improve VEGFR-targeting therapies, such as combination treatments, the development of more selective inhibitors, and the use of biomarkers, are discussed as promising approaches to enhance treatment efficacy and outcomes. Full article

(This article belongs to the Special Issue Angiogenesis in Diseases: Molecular Mechanism and Regulation)

► Show Figures

Figure 1

21 pages, 15840 KiB

Open AccessArticle

Transcriptomic Analysis of the Negative Effect of Epigallocatechin-3-Gallate from Tea Plant (Camellia sinensis) on Agrobacterium-Mediated Transformation Efficiency

by Guizhi Liu, Na Tian, Lan Chen, Siyi Xie, Jinyu Hu, Qifang Jin, Chenyu Shao, Mengdi Huang, Qin Su, Jianan Huang, Zhonghua Liu and Shuoqian Liu

Curr. Issues Mol. Biol. 2025, 47(3), 178; https://doi.org/10.3390/cimb47030178 - 8 Mar 2025

Abstract

Agrobacterium-mediated transformation is a widely used method for plant genetic modification. However, its efficiency in tea plants is notably low, and the underlying molecular mechanisms remain unclear, hindering advancements in the molecular breeding and biology of tea plants. In this study, tobacco [...] Read more.

Agrobacterium-mediated transformation is a widely used method for plant genetic modification. However, its efficiency in tea plants is notably low, and the underlying molecular mechanisms remain unclear, hindering advancements in the molecular breeding and biology of tea plants. In this study, tobacco was utilized as a model to investigate the effects of various concentrations of epigallocatechin-3-gallate (EGCG) on Agrobacterium transformation efficiency. The results demonstrated that at an EGCG concentration of 0.4 mg/mL, Agrobacterium nearly lost its ability to transform tobacco. Additionally, malondialdehyde content in Agrobacterium was measured before and after EGCG treatment. The findings indicated that EGCG treatment led to an increase in malondialdehyde content. Transcriptome sequencing analysis revealed that differentially expressed genes (DEGs) involved in Agrobacterium flagellar synthesis and secretion systems were down-regulated under EGCG stress. Furthermore, flgE, virB4, and virB6 were identified as hub genes through weighted gene co-expression network analysis (WGCNA). These results elucidate the dynamic mechanisms by which EGCG affects Agrobacterium at both the physicochemical and molecular levels, providing a theoretical basis for optimizing genetic transformation in tea plants. Full article

(This article belongs to the Section Molecular Plant Sciences)

► Show Figures

Figure 1

19 pages, 1282 KiB

Open AccessReview

Chemical Seed Priming: Molecules and Mechanisms for Enhancing Plant Germination, Growth, and Stress Tolerance

by Mason T. MacDonald and Vijaya R. Mohan

Curr. Issues Mol. Biol. 2025, 47(3), 177; https://doi.org/10.3390/cimb47030177 - 7 Mar 2025

Abstract

Food security is one of the world’s top challenges, specifically considering global issues like climate change. Seed priming is one strategy to improve crop production, typically via increased germination, yields, and/or stress tolerance. Hydropriming, or soaking seeds in water only, is the simplest [...] Read more.

Food security is one of the world’s top challenges, specifically considering global issues like climate change. Seed priming is one strategy to improve crop production, typically via increased germination, yields, and/or stress tolerance. Hydropriming, or soaking seeds in water only, is the simplest form of seed priming. However, the addition of certain seed priming agents has resulted in a variety of modified strategies, including osmopriming, halopriming, hormonal priming, PGR priming, nutripriming, and others. Most current research has focused on hormonal and nutripriming. This review will focus on the specific compounds that have been used most often over the past 3 years and the physiological effects that they have had on crops. Over half of recent research has focused on four compounds: (1) salicylic acid, (2) zinc, (3) gibberellic acid, and (4) potassium nitrate. One of the most interesting characteristics of all chemical seed priming agents is that they are exposed only to seeds yet confer benefits throughout plant development. In some cases, such benefits have been passed to subsequent generations, suggesting an epigenetic effect, which is supported by observed changes in DNA methylation and histone modification. This review will summarize the current state of knowledge on molecular changes and physiological mechanisms associated with chemical seed priming agents and discuss avenues for future research. Full article

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

► Show Figures

Figure 1

29 pages, 1249 KiB

Open AccessReview

The Application and Molecular Mechanisms of Mitochondria-Targeted Antioxidants in Chemotherapy-Induced Cardiac Injury

by Chih-Jen Liu, Lu-Kai Wang and Fu-Ming Tsai

Curr. Issues Mol. Biol. 2025, 47(3), 176; https://doi.org/10.3390/cimb47030176 - 7 Mar 2025

Abstract

Chemotherapeutic agents play a crucial role in cancer treatment. However, their use is often associated with significant adverse effects, particularly cardiotoxicity. Drugs such as anthracyclines (e.g., doxorubicin) and platinum-based agents (e.g., cisplatin) cause mitochondrial damage, which is one of the main mechanisms underlying [...] Read more.

Chemotherapeutic agents play a crucial role in cancer treatment. However, their use is often associated with significant adverse effects, particularly cardiotoxicity. Drugs such as anthracyclines (e.g., doxorubicin) and platinum-based agents (e.g., cisplatin) cause mitochondrial damage, which is one of the main mechanisms underlying cardiotoxicity. These drugs induce oxidative stress, leading to an increase in reactive oxygen species (ROS), which in turn damage the mitochondria in cardiomyocytes, resulting in impaired cardiac function and heart failure. Mitochondria-targeted antioxidants (MTAs) have emerged as a promising cardioprotective strategy, offering a potential solution. These agents efficiently scavenge ROS within the mitochondria, protecting cardiomyocytes from oxidative damage. Recent studies have shown that MTAs, such as elamipretide, SkQ1, CoQ10, and melatonin, significantly mitigate chemotherapy-induced cardiotoxicity. These antioxidants not only reduce oxidative damage but also help maintain mitochondrial structure and function, stabilize mitochondrial membrane potential, and prevent excessive opening of the mitochondrial permeability transition pore, thus preventing apoptosis and cardiac dysfunction. In this review, we integrate recent findings to elucidate the mechanisms of chemotherapy-induced cardiotoxicity and highlight the substantial therapeutic potential of MTAs in reducing chemotherapy-induced heart damage. These agents are expected to offer safer and more effective treatment options for cancer patients in clinical practice. Full article

(This article belongs to the Topic Molecular and Cellular Mechanisms of Heart Disease)

► Show Figures

Figure 1

28 pages, 1936 KiB

Open AccessReview

Innovation in Osteogenesis Activation: Role of Marine-Derived Materials in Bone Regeneration

by Maria Giovanna Rizzo, Marilena Briglia, Vincenzo Zammuto, Dario Morganti, Caterina Faggio, Federica Impellitteri, Cristiana Roberta Multisanti and Adriana Carol Eleonora Graziano

Curr. Issues Mol. Biol. 2025, 47(3), 175; https://doi.org/10.3390/cimb47030175 - 7 Mar 2025

Abstract

Marine-derived biomaterials are emerging as promising candidates for tissue regeneration due to their sustainability, biocompatibility, bioactivity, and unique chemical structure. This review provides an overview of different marine-derived inorganic and organic materials, such as calcium carbonate, magnesium salts, silica, polysaccharides, bioactive peptides, and [...] Read more.

Marine-derived biomaterials are emerging as promising candidates for tissue regeneration due to their sustainability, biocompatibility, bioactivity, and unique chemical structure. This review provides an overview of different marine-derived inorganic and organic materials, such as calcium carbonate, magnesium salts, silica, polysaccharides, bioactive peptides, and lipid-based compounds, and their effects in promoting osteogenesis. Specifically, the osteoinductive, osteoconductive, and osteointegrative activities of traditional and innovative materials that influence key molecular pathways such as BMP/Smad and Wnt/β-catenin signaling underlying bone formation will be evaluated. This review also prospects innovative approaches, i.e., phage display technology, to optimize marine-derived peptides for targeted bone regeneration. In the context of innovative and sustainable materials, this review suggests some interesting applications of unusual materials able to overcome the limitations of conventional ones and stimulate cellular regeneration of bone tissue by activating specific molecular pathways. Full article

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

► Show Figures

Graphical abstract

16 pages, 1858 KiB

Open AccessArticle

Desmodesmus Extract as a Mitochondrion-Targeted Neuroprotective Agent in Parkinson’s Disease: An In Vitro Study

by Muazzez Derya-Andeden, Pinar Altin-Celik, Enver Ersoy Andeden and Hamiyet Donmez-Altuntas

Curr. Issues Mol. Biol. 2025, 47(3), 174; https://doi.org/10.3390/cimb47030174 - 6 Mar 2025

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease, and its prevalence is expected to double in the next 30 years. Currently, no effective treatment exists for Parkinson’s disease. Thus, the research has focused on discovering new natural compounds with strong neuroprotective [...] Read more.

Parkinson’s disease (PD) is the second most common neurodegenerative disease, and its prevalence is expected to double in the next 30 years. Currently, no effective treatment exists for Parkinson’s disease. Thus, the research has focused on discovering new natural compounds with strong neuroprotective potential. This study aimed to investigate the effects of the methanol extract of Desmodesmus arthrodesmiformis EM13 (DaMe) on the mitochondrial damage pathway in an in vitro model of PD. The isolate of Desmodesmus arthrodesmiformis EM13 was first grown under appropriate culture conditions, and then the extract (DaMe) was prepared for use in the experiments. The total lipid and protein contents, fatty acid composition, and elemental content of DaMe were subsequently determined. Human SH-SY5Y neuroblastoma cells were pretreated with nontoxic concentrations of DaMe before 6-hydroxydopamine (6-OHDA) toxicity. Pretreatment with DaMe at concentrations of 100, 250, and 500 µg/mL showed a neuroprotective effect on 6-OHDA-induced SH-SY5Y neuroblastoma cells by decreasing the reactive oxygen species (ROS) production, decreasing the total oxidant status (TOS), increasing the total antioxidant capacity (TAC), increasing the mitochondrial membrane potential (ΔΨm), decreasing the oxidative DNA damage, and regulating gene expressions related to PD and apoptosis. Given the results of our study, we suggest that DaMe can be used as a natural source for producing drugs and dietary supplements intended to treat PD. Full article

(This article belongs to the Special Issue Microalga Biotechnology and Applications: Molecular and Cellular Mechanisms)

► Show Figures

Graphical abstract

24 pages, 6081 KiB

Open AccessArticle

Exploring the Therapeutic Potential of the DOT1L Inhibitor EPZ004777 Using Bioinformatics and Molecular Docking Approaches in Acute Myeloid Leukemia

by Mehmet Kivrak, Ihsan Nalkiran and Hatice Sevim Nalkiran

Curr. Issues Mol. Biol. 2025, 47(3), 173; https://doi.org/10.3390/cimb47030173 - 4 Mar 2025

Abstract

Background: Acute myeloid leukemia (AML) is a malignancy characterized by the clonal expansion of hematopoietic stem and progenitor cells, often associated with mutations such as NPM1. DOT1L inhibitors have shown potential as new therapeutic opportunities for NPM1-mutant AML. The aim of this study [...] Read more.

Background: Acute myeloid leukemia (AML) is a malignancy characterized by the clonal expansion of hematopoietic stem and progenitor cells, often associated with mutations such as NPM1. DOT1L inhibitors have shown potential as new therapeutic opportunities for NPM1-mutant AML. The aim of this study was to investigate potential alternative targets of the small-molecule inhibitor EPZ004777, in addition to its primary target, DOT1L, using RNA sequencing data from the NCBI-GEO database (GSE85107). Methods: Differentially expressed genes (DEGs) were identified through bioinformatic analysis, followed by pathway enrichment analysis to uncover the relevant biological pathways. Additionally, molecular docking analysis was conducted to assess the binding affinity of EPZ004777 with the proteins CT45A3, HOXA4, SNX19, TPBG, and ZNF185, which were identified as significantly DEGs. The protein structures were obtained from AlphaFold and the Protein Data Bank. Results: EPZ004777 significantly altered gene expression. Oncofetal genes (CT45A3, TPBG) and genes associated with oncogenic pathways (HOXA4, ZNF185, SNX19) were downregulated, while the pro-apoptotic gene BEX3 was upregulated. Pathway enrichment analysis revealed the suppression of the Rap1 signaling pathway and cell adhesion molecules, which may reduce the invasiveness of AML cells. Additionally, upregulation of immune-related pathways suggests enhanced anti-tumor immune responses. Molecular docking analysis demonstrated that EPZ004777 has strong binding potential with SNX19, TPBG, and ZNF185 proteins. Conclusions: EPZ004777 has been identified as a potent modulator of SNX19, TPBG, and ZNF185 associated with apoptosis and tumor progression in AML. Full article

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

► Show Figures

Figure 1

29 pages, 3950 KiB

Open AccessReview

Multi-Pathway Study for Oxaliplatin Resistance Reduction

by Tong Ye, Chen Wu, Jintong Na, Xiyu Liu and Yong Huang

Curr. Issues Mol. Biol. 2025, 47(3), 172; https://doi.org/10.3390/cimb47030172 - 4 Mar 2025

Abstract

Chemotherapy for cancer frequently uses platinum-based medications, including oxaliplatin, carboplatin, and cisplatin; however, due to their high systemic toxicity, lack of selectivity, drug resistance, and other side effects, platinum-based medications have very limited clinical application. As a first-line medication in antitumor therapy, oxaliplatin [...] Read more.

Chemotherapy for cancer frequently uses platinum-based medications, including oxaliplatin, carboplatin, and cisplatin; however, due to their high systemic toxicity, lack of selectivity, drug resistance, and other side effects, platinum-based medications have very limited clinical application. As a first-line medication in antitumor therapy, oxaliplatin must be administered to minimize side effects while achieving anticancer objectives. A new CDC7 inhibitor called XL413 has demonstrated promising antitumor therapeutic effects in a variety of malignant tumors and may have anticancer properties. This offers a fresh viewpoint on how to lessen oxaliplatin resistance and, specifically, increase the potency of already prescribed anticancer therapies. In this paper, the current developments in anticancer therapy are discussed, along with the many mechanisms of oxaliplatin’s antitumor effects, clinical treatment challenges, and related approaches. We conducted more research on oxaliplatin resistance that arose during chemotherapy and searched for ways to lessen it in order to enhance its chemotherapeutic performance. Ultimately, we studied how distinct resistance routes relate to one another. Meanwhile, XL413, a novel CDC7 inhibitor, offers a perspective on the possibilities for developing treatment approaches for this innovation point. The search terms “Oxaliplatin, XL413, drug resistance, cancer treatment,” etc., were applied in the X-MOL and PubMed databases for this review’s literature search. Boolean logic was then employed to maximize the search approach. These databases can offer thorough research data and cover a broad range of biological publications. Excluded publications were works of low relevance, duplicates, or those with insufficient information. The mechanism of oxaliplatin’s anticancer effect, oxaliplatin resistance and its amelioration, and the role of XL413 in oxaliplatin treatment were the main topics of the 140 publications that were ultimately included for analysis. Full article

(This article belongs to the Special Issue Drugs: Mechanisms of Action, Molecular Targets and Biological Activities, 2nd Edition)

► Show Figures

Graphical abstract

24 pages, 3157 KiB

Open AccessArticle

Comparative Transcriptome Analysis of Two Types of Rye Under Low-Temperature Stress

by Haonan Li, Jiahuan Zhao, Weiyong Zhang, Ting He, Dexu Meng, Yue Lu, Shuge Zhou, Xiaoping Wang and Haibin Zhao

Curr. Issues Mol. Biol. 2025, 47(3), 171; https://doi.org/10.3390/cimb47030171 - 3 Mar 2025

Abstract

Wheat is a crucial food crop, and low-temperature stress can severely disrupt its growth and development, ultimately leading to a substantial reduction in wheat yield. Understanding the cold-resistant genes of wheat and their action pathways is essential for revealing the cold-resistance mechanism of [...] Read more.

Wheat is a crucial food crop, and low-temperature stress can severely disrupt its growth and development, ultimately leading to a substantial reduction in wheat yield. Understanding the cold-resistant genes of wheat and their action pathways is essential for revealing the cold-resistance mechanism of wheat, enhancing its yield and quality in low-temperature environments, and ensuring global food security. Rye (Secale cereale L.), on the other hand, has excellent cold resistance in comparison to some other crops. By studying the differential responses of different rye varieties to low-temperature stress at the transcriptome level, we aim to identify key genes and regulatory mechanisms related to cold tolerance. This knowledge can not only deepen our understanding of the molecular basis of rye’s cold resistance but also provide valuable insights for improving the cold tolerance of other crops through genetic breeding strategies. In this study, young leaves of two rye varieties, namely “winter” rye and “victory” rye, were used as experimental materials. Leaf samples of both types were treated at 4 °C for 0, 6, 24, and 72 h and then underwent RNA-sequencing. A total of 144,371 Unigenes were reconstituted. The Unigenes annotated in the NR, GO, KEGG, and KOG databases accounted for 79.39%, 55.98%, 59.90%, and 56.28%, respectively. A total of 3013 Unigenes were annotated as transcription factors (TFs), mainly belonging to the MYB family and the bHLH family. A total of 122,065 differentially expressed genes (DEGs) were identified and annotated in the GO pathways and KEGG pathways. For DEG analysis, 0 h 4 °C treated samples were controls. With strict criteria (p < 0.05, fold-change > 2 or <0.5, |log₂(fold-change)| > 1), 122,065 DEGs were identified and annotated in GO and KEGG pathways. Among them, the “Chloroplast thylakoid membrane” and “Chloroplast” pathways were enriched in both the “winter” rye and “victory” rye groups treated with low temperatures, but the degrees of significance were different. Compared with “victory” rye, “winter” rye has more annotated pathways such as the “hydrogen catabolic process”. Although the presence of more pathways does not directly prove a more extensive cold-resistant mechanism, these pathways are likely associated with cold tolerance. Our subsequent analysis of gene expression patterns within these pathways, as well as their relationships with known cold-resistance-related genes, suggests that they play important roles in “winter” rye’s response to low-temperature stress. For example, genes in the “hydrogen catabolic process” pathway may be involved in regulating cellular redox balance, which is crucial for maintaining cell function under cold stress. Full article

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

► Show Figures

Figure 1

18 pages, 5915 KiB

Open AccessArticle

In Silico Analysis of miRNA-Regulated Pathways in Spinocerebellar Ataxia Type 7

by Verónica Marusa Borgonio-Cuadra, Aranza Meza-Dorantes, Nonanzit Pérez-Hernández, José Manuel Rodríguez-Pérez and Jonathan J. Magaña

Curr. Issues Mol. Biol. 2025, 47(3), 170; https://doi.org/10.3390/cimb47030170 - 2 Mar 2025

Abstract

Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disease characterized by cerebellar ataxia and retinal degeneration, caused by an abnormal expansion of the CAG trinucleotide in the coding region of the ATXN7 gene. Currently, in silico analysis is used to explore mechanisms [...] Read more.

Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disease characterized by cerebellar ataxia and retinal degeneration, caused by an abnormal expansion of the CAG trinucleotide in the coding region of the ATXN7 gene. Currently, in silico analysis is used to explore mechanisms and biological processes through bioinformatics predictions in various neurodegenerative diseases. Therefore, the aim of this study was to identify candidate human gene targets of four miRNAs (hsa-miR-29a-3p, hsa-miR-132-3p, hsa-miR-25-3p, and hsa-miR-92a-3p) involved in pathways that could play an important role in SCA7 pathogenesis through comprehensive in silico analysis including the prediction of miRNA target genes, Gen Ontology enrichment, identification of core genes in KEGG pathways, transcription factors and validated miRNA target genes with the mouse SCA7 transcriptome data. Our results showed the participation of the following pathways: adherens junction, focal adhesion, neurotrophin signaling, endoplasmic reticulum processing, actin cytoskeleton regulation, RNA transport, and apoptosis and dopaminergic synapse. In conclusion, unlike previous studies, we highlight using a bioinformatics approach the core genes and transcription factors involved in the different biological pathways and which ones are targets for the four miRNAs, which, in addition to being associated with neurodegenerative diseases, are also de-regulated in the plasma of patients with SCA7. Full article

(This article belongs to the Special Issue Cellular and Molecular Biology Insights into Neurodegenerative Diseases: From Pathogenesis to Therapeutic Targets)

► Show Figures

Figure 1

18 pages, 1700 KiB

Open AccessArticle

In Silico Detection of Virulence Genes in Whole-Genome Sequences of Extra-Intestinal Pathogenic Escherichia coli (ExPEC) Documented in Countries of the Andean Community

by Nabila Aldaz, Karen Loaiza, César Marcelo Larrea-Álvarez, Miroslava Anna Šefcová and Marco Larrea-Álvarez

Curr. Issues Mol. Biol. 2025, 47(3), 169; https://doi.org/10.3390/cimb47030169 - 2 Mar 2025

Abstract

E. coli pathotypes, which cause extra-intestinal infections, pose significant public health challenges, emphasizing the need for virulence gene surveillance to understand their dynamics. Key virulence genes have been identified in E. coli from Andean community countries, predominantly linked to human and animal sources. [...] Read more.

E. coli pathotypes, which cause extra-intestinal infections, pose significant public health challenges, emphasizing the need for virulence gene surveillance to understand their dynamics. Key virulence genes have been identified in E. coli from Andean community countries, predominantly linked to human and animal sources. However, detailed data on virulence profiles from environmental and food sources remain limited. This study utilized an in silico approach to analyze 2402 whole-genome sequences from EnteroBase, known for associations with antimicrobial resistance genes. Of the isolates, 30% were classified as ExPEC, averaging 39 virulence genes per isolate, with adhesin-related genes being the most predominant. These findings were consistent across human, environmental, animal, and food samples. Human and animal isolates exhibited greater diversity in adhesin, secreted factors, and toxin genes compared to other sources, whereas food samples contained the fewest factors. ST449 isolates exhibited an average of 50 virulence genes per genome, with secreted factors and adhesins equally represented, while ST131, ST38, and ST10 carried around 40 genes, predominantly adhesins. Overall, the diversity and frequency of virulence genes exceeded prior reports in the region, highlighting the importance of monitoring these traits to identify emerging patterns in pathogenic E. coli strains frequently subjected to antibiotic exposure. Full article

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

► Show Figures

Figure 1

Journal Description

Current Issues in Molecular Biology

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI