Current Issues in Molecular Biology

30 pages, 6234 KiB

Open AccessArticle

Molecular Effects of Cornelian Cherry Fruit (Cornus mas L.) Extract on Sleep Deprivation-Induced Oxidative Stress, Cytokine Dysregulation, and Behavioural Changes in Wistar Rats

by Vlad Sever Neculicioiu, Ioana Colosi, Alexandra Sevastre-Berghian, Dan Alexandru Toc, Horațiu Alexandru Colosi, Luminita David, Mara Muntean, Remus Moldovan, Ana-Maria Vlase, Vlad Alexandru Toma, Carmen Costache, Şoimiţa Mihaela Suciu and Simona Clichici

Curr. Issues Mol. Biol. 2025, 47(6), 399; https://doi.org/10.3390/cimb47060399 - 28 May 2025

Abstract

Sleep deprivation (SD) induces significant neurobiological changes, including oxidative stress, neuroinflammation, and behavioural impairments. This study was designed as a proof of concept to assess the potential for modulating the effects of SD through a short-term seven-day administration of Cornus mas (C. [...] Read more.

Sleep deprivation (SD) induces significant neurobiological changes, including oxidative stress, neuroinflammation, and behavioural impairments. This study was designed as a proof of concept to assess the potential for modulating the effects of SD through a short-term seven-day administration of Cornus mas (C. mas) in a rapid eye movement (REM) SD rodent paradigm. Adult male Wistar rats were randomised in four groups (n = 7): control, C. mas (CM), sleep deprivation (SD), and sleep deprivation with C. mas (SD + CM). Behaviourally, SD induced hyperactivity and hyperlocomotion. SD determined histological alterations in the prefrontal cortex and corpus callosum myelin coupled with ultrastructural mitochondrial and cellular abnormalities in the prefrontal cortex, hippocampus, and pineal gland. Despite evidence of systemic oxidative stress coupled with decreased serum GABA and BDNF following SD, no significant changes were observed in redox markers or inflammatory cytokine levels (TNF-α, IL-1β) within the prefrontal cortex or hippocampus. C. mas extract has shown an overall modest modulatory action, mainly evidenced on behavioural, histological, and ultrastructural parameters. Taken together, these findings highlight behavioural changes and region-specific molecular and structural abnormalities following prolonged REM SD in rats. Full article

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

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17 pages, 8775 KiB

Open AccessArticle

Genome-Wide Characterization of the Heat Shock Transcription Factor Gene Family in Begonia semperflorens Reveals Promising Candidates for Heat Tolerance

by Zhirou Liu, Nan Lin, Qirui Wang, Enkai Xu and Kaiming Zhang

Curr. Issues Mol. Biol. 2025, 47(6), 398; https://doi.org/10.3390/cimb47060398 - 27 May 2025

Abstract

Begonia semperflorens (B. semperflorens) is a popular ornamental plant widely used in landscapes such as plazas and flower beds, and it is also commonly grown as a potted plant indoors. It is known for its adaptability to high temperatures, drought, and [...] Read more.

Begonia semperflorens (B. semperflorens) is a popular ornamental plant widely used in landscapes such as plazas and flower beds, and it is also commonly grown as a potted plant indoors. It is known for its adaptability to high temperatures, drought, and shade. Under heat-tolerant conditions, heat shock transcription factors (HSFs) are key transcriptional regulatory proteins that play crucial roles in cellular processes. Despite extensive studies on the HSF family in various species, there has been no specific analysis targeting B. semperflorens. In this study, we identified 37 members of the BsHSF gene family in B. semperflorens based on its genome scaffold, which are unevenly distributed across the genome. Phylogenetic analysis reveals that these 37 members can be divided into three subfamilies. Analysis of their physicochemical properties shows significant diversity among these proteins. Except for the BsHSFB7 protein located in the cytoplasm, all other BsHSF proteins were found to be nuclear-localized. A comparison of the amino acid sequences indicates that all BsHSF proteins contain a conserved DNA-binding domain structure. Analysis of the promoter cis-acting elements also suggests that BsHSFs may be associated with heat stress and plant secondary metabolism. We further investigated the duplication events of BsHSF genes and their collinearity with genes from other Begonia species. Finally, through real-time quantitative PCR, we examined the expression patterns of the 37 BsHSFs in different plant tissues (roots, stems, leaves, and flowers) and their expression levels under heat stress treatment. The results show that, except for BsHSF29, all BsHSFs were expressed in various tissues, with varying expression levels across tissues. Except for BsHSF33 and BsHSF34, the expression levels of almost all BsHSF genes increased in response to heat treatment. In summary, these findings provide a better understanding of the role and regulatory mechanisms of HSFs in the heat stress response of B. semperflorens and lay the foundation for further exploration of the biological functions of BsHSFs in the stress responses of B. semperflorens. Full article

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

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14 pages, 949 KiB

Open AccessArticle

Hypermethylation of SOX1 and HOXA9 Genes Is Associated with Clinicopathologic Characteristics of Non-Small Cell Lung Cancer Patients

by Milica Kontić, Mihailo Stjepanović and Filip Marković

Curr. Issues Mol. Biol. 2025, 47(6), 397; https://doi.org/10.3390/cimb47060397 - 26 May 2025

Abstract

DNA methylation changes, especially hypermethylation of SOX1 and HOXA9, may serve as biomarkers for diagnosis and prognosis in non-small cell lung carcinoma (NSCLC). This study analyzed the methylation status of SOX1 and HOXA9 in 63 primary NSCLC tumor samples, corresponding normal lung tissues, [...] Read more.

DNA methylation changes, especially hypermethylation of SOX1 and HOXA9, may serve as biomarkers for diagnosis and prognosis in non-small cell lung carcinoma (NSCLC). This study analyzed the methylation status of SOX1 and HOXA9 in 63 primary NSCLC tumor samples, corresponding normal lung tissues, and circulating blood, using bisulfite pyrosequencing. The relationship between methylation patterns and clinicopathologic features was also explored. SOX1 and HOXA9 promoter methylation levels were significantly higher in tumor tissues compared to normal lung tissues and blood samples. Histological subtypes influenced methylation patterns, with squamous cell carcinomas (SCC) showing higher hypermethylation rates at both loci compared to other NSCLC subtypes. HOXA9 hypermethylation was associated with advanced tumor stage (stages II and III). Gender and smoking status did not correlate with methylation status. These findings highlight the cancer-specific nature of SOX1 and HOXA9 hypermethylation in NSCLC. Further investigation into demographic and molecular factors influencing methylation could enhance the clinical utility of SOX1 and HOXA9 in NSCLC diagnosis and management. Full article

(This article belongs to the Section Molecular Medicine)

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22 pages, 2392 KiB

Open AccessArticle

Insertional Mutagenesis as a Strategy to Open New Paths in Microalgal Molybdenum and Nitrate Homeostasis

by Esperanza Leon-Miranda, Manuel Tejada-Jimenez and Angel Llamas

Curr. Issues Mol. Biol. 2025, 47(6), 396; https://doi.org/10.3390/cimb47060396 - 26 May 2025

Abstract

Molybdenum (Mo) is a vital micronutrient for nearly all living organisms, serving as a cofactor for molybdoenzymes that catalyze essential redox reactions in nitrogen metabolism. Among these enzymes, nitrate reductase plays a crucial role in nitrate assimilation. Maintaining Mo homeostasis—including uptake, storage, and [...] Read more.

Molybdenum (Mo) is a vital micronutrient for nearly all living organisms, serving as a cofactor for molybdoenzymes that catalyze essential redox reactions in nitrogen metabolism. Among these enzymes, nitrate reductase plays a crucial role in nitrate assimilation. Maintaining Mo homeostasis—including uptake, storage, and utilization—is critical to avoid both deficiency and toxicity. Our research focuses on uncovering novel molecular components involved in Mo homeostasis, particularly in connection with nitrate assimilation, using Chlamydomonas reinhardtii, a model green microalga. To achieve this, we generated more than 5000 Chlamydomonas transformants through insertional mutagenesis using a paromomycin resistance cassette (AphVIII) and screened them for altered growth on nitrate and under different Mo concentrations. We identified four strains showing altered growth patterns when using nitrate as a nitrogen source or exhibiting increased sensitivity or resistance to Mo. The genomic alterations in these strains were identified. Notably, both a Mo-resistant and a Mo-sensitive transformant had disruptions in the genes that encoded ABC-type transport proteins, indicating a potential role for these proteins in Mo transport. Additionally, two strains were unable to grow on nitrate. One of them had a mutation in the CNX7, a gene involved in Mo cofactor biosynthesis, while the other had a mutation in BAT1, an amino acid transporter. The BAT1 mutant represents an interesting case study, as this gene has not previously been associated with nitrate metabolism. These findings enhance our understanding of Mo and nitrate homeostasis mechanisms and open new paths for engineering microalgae with improved nitrogen assimilation. Full article

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

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14 pages, 5621 KiB

Open AccessArticle

Differential Expression of lncRNAs in Ovarian Tissue of Meigu Goats During the Sexually Immature and Mature Periods

by Juntao Li, Yanan Xue, Tao Zhong, Linjie Wang, Li Li, Hongping Zhang and Siyuan Zhan

Curr. Issues Mol. Biol. 2025, 47(6), 395; https://doi.org/10.3390/cimb47060395 - 26 May 2025

Abstract

The ovary is the primary reproductive organ in goats, and its development significantly influences the sexual maturity and reproductive capacity of individuals. Long non-coding RNAs (lncRNAs) are integral to a wide array of biological processes. However, the regulatory function of lncRNAs in the [...] Read more.

The ovary is the primary reproductive organ in goats, and its development significantly influences the sexual maturity and reproductive capacity of individuals. Long non-coding RNAs (lncRNAs) are integral to a wide array of biological processes. However, the regulatory function of lncRNAs in the development of ovarian tissue during sexual maturity in goats remains largely unexplored. In this study, we conducted RNA sequencing on ovarian tissue samples from Meigu goats at sexually immature (3 months, n = 3) and sexually mature periods (6 months, n = 3). We identified a total of 966 lncRNAs across six libraries, with 95 lncRNAs exhibiting differential expression. Additionally, we identified the target genes of these DElncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these target genes were associated with various biological processes and pathways pertinent to ovarian development, including reproduction, reproductive process, JAK-STAT signaling pathway, progesterone-mediated oocyte maturation, Wnt signaling pathway, and cytokine–cytokine receptor interaction. Furthermore, lncRNA–mRNA interaction network analysis suggested that MSTRG.15120.9 and MSTRG.15110.2 play crucial regulatory roles in ovarian development. This study provides a valuable resource for elucidating the molecular regulatory mechanisms of lncRNAs in ovarian tissue during the sexual maturity period in goats. Full article

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

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15 pages, 3646 KiB

Open AccessArticle

Could Fingolimod Combined with Bevacizumab Be a New Hope in Glioblastoma Treatment?

by Murat Baloglu, Canan Vejselova Sezer, Hüseyin Izgördü, Ibrahim Yilmaz and Hatice Mehtap Kutlu

Curr. Issues Mol. Biol. 2025, 47(6), 394; https://doi.org/10.3390/cimb47060394 - 26 May 2025

Abstract

Glioblastoma, classified as a grade IV astrocytoma, is an aggressive and malignant primary brain tumor with no known cure. Despite the implementation of standard medical and surgical treatment protocols, the disease often progresses with unsatisfactory outcomes. This study aimed to evaluate the cytotoxic, [...] Read more.

Glioblastoma, classified as a grade IV astrocytoma, is an aggressive and malignant primary brain tumor with no known cure. Despite the implementation of standard medical and surgical treatment protocols, the disease often progresses with unsatisfactory outcomes. This study aimed to evaluate the cytotoxic, proapoptotic, and antimetastatic effects of anti-angiogenic monoclonal antibody bevacizumab combined with the sphingosine-1-phosphate receptor modulator fingolimod on rat glioma C6 cells. The cytotoxicity of bevacizumab and fingolimod was evaluated using the MTT assay. Proapoptotic activity was assessed through flow cytometric analyses, including Annexin V–FITC staining, caspase 3/7 activation, and mitochondrial membrane potential measurements. Morphological changes were examined using confocal microscopy. Antimetastatic effects were evaluated via anti-migration and colony formation assays. The combination of bevacizumab and fingolimod exhibited antiproliferative, cytotoxic, proapoptotic, and antimetastatic effects on C6 glioma cells at low IC₅₀ concentrations. Based on growth inhibitory, proapoptotic, and antimetastatic activities on C6 glioma cells, the combination of bevacizumab and fingolimod demonstrates significant growth-inhibitory, proapoptotic, and antimetastatic activities against C6 glioma cells, suggesting its potential as a promising pharmacotherapeutic approach for the treatment of glioblastoma. Full article

(This article belongs to the Section Molecular Pharmacology)

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32 pages, 1396 KiB

Open AccessReview

An Analysis of Three Pistacia Species’ Phenolic Compounds and Their Potential Anticancer and Cytotoxic Activities on Cancer Cells—A Review

by Naser A. Alsharairi

Curr. Issues Mol. Biol. 2025, 47(6), 393; https://doi.org/10.3390/cimb47060393 - 26 May 2025

Abstract

The genus Pistacia from the Anacardiaceae family contains species of wild flowering plants. The only species that produces edible nuts large enough for commercial sale is P. vera L. (pistachio). Other species, such as P. terebinthus L., P. atlantica L., and P. khinjuk [...] Read more.

The genus Pistacia from the Anacardiaceae family contains species of wild flowering plants. The only species that produces edible nuts large enough for commercial sale is P. vera L. (pistachio). Other species, such as P. terebinthus L., P. atlantica L., and P. khinjuk, are used as pistachio rootstocks. Pistacia species include phenolic compounds, such as flavonoids, essential oils, and tannins, which are responsible for a number of pharmacological properties. The species most commonly investigated for their anticancer and/or cytotoxic activities against cancer cells in experimental studies include P. lentiscus, P. atlantica subspecies, and P. chinensis subsp. integerrima. However, no review exists that evaluates the phenolic compounds of three other Pistacia species (P. vera L., P. terebinthus L., and P. khinjuk) and their anticancer and cytotoxic effects. Thus, this review aims to thoroughly assess the phenolic compounds that were isolated from these species and investigate any potential anticancer or cytotoxic effects on cancer cells. The findings show that pistacia species and their isolated phenolic compounds (phenolic acids, flavonoids, and essential oils) from different plant parts have anticancer activity against lung, cervical, prostate, gastric, colon, liver, renal, skin, and breast cancer cells. Additionally, certain phenolic compounds from pistacia species have cytotoxic activity; however, the degree of toxicity may vary based on the dosage and duration of use. Further experiments are required to fully understand the possible mechanisms underlying the anticancer and cytotoxic effects of pistacia species and their phenolic compounds on cancer cells. Full article

(This article belongs to the Special Issue Targeted Therapeutic Approaches in Cancer: Combining Natural Compounds and Conventional Drugs)

20 pages, 2001 KiB

Open AccessArticle

Testing Protein Stress Signals in Peripheral Immunocytes Under the Same Treatment Capable of Decreasing the Incidence of Alzheimer’s Disease in Bladder Cancer Patients

by Benjamin Y. Klein, Ofer N. Gofrit and Charles L. Greenblatt

Curr. Issues Mol. Biol. 2025, 47(6), 392; https://doi.org/10.3390/cimb47060392 - 26 May 2025

Abstract

Several studies showed that the incidence of Alzheimer’s disease (AD) is significantly lower in patients with non-muscle invasive bladder cancer (NMIBC) treated with intravesical bacillus Calmette–Guérin (BCG) instillations compared to treatment by alternative methods. Hypothetically, failure to clear misfolded and aggregated proteins (i.e., [...] Read more.

Several studies showed that the incidence of Alzheimer’s disease (AD) is significantly lower in patients with non-muscle invasive bladder cancer (NMIBC) treated with intravesical bacillus Calmette–Guérin (BCG) instillations compared to treatment by alternative methods. Hypothetically, failure to clear misfolded and aggregated proteins (i.e., beta-amyloid) in AD brains and peripheral blood mononuclear cells (PBMCs) implicates BCG in upgrading the unfolded protein response (UPR). To test this hypothesis, pre- versus post-BCG PBMC proteins of the UPR pathway were compared in six NMIBC patients by capillary immunoelectrophoresis on an Abby instrument. PERK, the endoplasmic reticulum (ER) resident kinase, a stress-activated sensor, and its substrate alpha component of the eIF2 translation factor (eIF2a) complex inactivation were considered as potentially proapoptotic via a downstream proapoptotic transcription factor only if persistently high. GAPDH, a glycolytic marker of innate immunocyte training by BCG, and eight other UPR proteins were considered antiapoptotic. Summation of antiapoptotic %change scores per patient showed that the older the age, the lower the antiapoptotic %change. Higher antiapoptotic scores were observed upon a longer time from BCG treatment (with the exception of the patient in her ninth decade of life). Studies with more individuals could substantiate that BCG enhances the antiapoptotic aggregate-clearance effect of the UPR in PBMCs of NMIBC patients, which hypothetically protects brain cells against AD. Full article

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

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15 pages, 10924 KiB

Open AccessArticle

FBXO10 Drives Hepatocellular Carcinoma Proliferation via K63-Linked Ubiquitination and Stabilization of FRMPD1

by Wuguang Liu, Bin Xu, Kashif Kifayat, Yuhong Xie, Xiaolong Liu, Chengyong Dong and Liming Wang

Curr. Issues Mol. Biol. 2025, 47(6), 391; https://doi.org/10.3390/cimb47060391 - 24 May 2025

Abstract

Aberrant ubiquitination drives hepatocellular carcinoma (HCC) progression, yet the role of FBXO10—a key F-box E3 ubiquitin ligase component—remains uncharacterized. Through bioinformatics analyses and functional validation, we establish FBXO10 as a critical oncogenic driver in HCC. Transcriptomic data from public databases (TIMER, UALCAN, GEO) [...] Read more.

Aberrant ubiquitination drives hepatocellular carcinoma (HCC) progression, yet the role of FBXO10—a key F-box E3 ubiquitin ligase component—remains uncharacterized. Through bioinformatics analyses and functional validation, we establish FBXO10 as a critical oncogenic driver in HCC. Transcriptomic data from public databases (TIMER, UALCAN, GEO) revealed significant FBXO10 upregulation in HCC tissues, with elevated expression predicting advanced tumor stage, metastasis, and reduced survival. Functionally, FBXO10 silencing suppressed HCC cell proliferation while its overexpression promoted tumor growth. Mechanistic studies revealed that FBXO10 directly interacts with FRMPD1 to mediate its K63-linked polyubiquitination and stabilization, independent of transcriptional regulation. FRMPD1 restoration rescued FBXO10-mediated proliferation, confirming its role as the key downstream effector. Clinically, FBXO10 expression correlated with TP53 mutations and adverse clinicopathological features. Our findings reveal a novel FBXO10–FRMPD1 axis promoting hepatocarcinogenesis through post-translational stabilization, positioning FBXO10 as both a prognostic biomarker and therapeutic target in HCC. Full article

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

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25 pages, 899 KiB

Open AccessReview

New Insights into the Interplay Between Simple Sugars and Liver Diseases

by Simona Parisse, Erika Coltorti, Monica Mischitelli, Flaminia Ferri and Stefano Ginanni Corradini

Curr. Issues Mol. Biol. 2025, 47(6), 390; https://doi.org/10.3390/cimb47060390 - 23 May 2025

Abstract

In hepatology, there is growing interest in identifying the mechanisms and risk factors underlying liver diseases with increasing incidence, with particular focus on metabolic dysfunction-associated steatotic liver disease (MASLD) and its complications. Simple sugars have been recognized as key contributors to liver injury [...] Read more.

In hepatology, there is growing interest in identifying the mechanisms and risk factors underlying liver diseases with increasing incidence, with particular focus on metabolic dysfunction-associated steatotic liver disease (MASLD) and its complications. Simple sugars have been recognized as key contributors to liver injury and disease progression, not only in the context of MASLD but also beyond. As a result, numerous studies have aimed to elucidate their role in liver pathophysiology. Specifically, simple sugars have been associated with pivotal mechanisms involved in the onset of liver diseases, including inflammation, de novo lipogenesis, oxidative stress, insulin resistance, and dysbiosis with increased intestinal permeability. These mechanisms collectively contribute to a significant association between simple sugar intake and liver diseases of varying stages and severity. The scientific evidence available to date has not only clarified potential pathogenic mechanisms and clinical correlations but also led to the identification of potential therapeutic targets, encompassing both lifestyle interventions and molecular approaches. This review aims to provide a comprehensive analysis of the associations between simple sugar intake, liver injury, and liver diseases. To this end, we conducted an extensive review of the literature, selecting the most relevant and up-to-date studies on the topic. Full article

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

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14 pages, 1475 KiB

Open AccessArticle

Anti-Inflammatory Effects of Amomum villosum Extract on Dextran Sodium Sulfate-Induced Colitis in Mice

by Han-Byeol Choi, Ryeo Won Kim, Gi-Sang Bae, Ji Hun Jang, Ye-Seul Kim, Byung Ouk Park and Kang-Beom Kwon

Curr. Issues Mol. Biol. 2025, 47(6), 389; https://doi.org/10.3390/cimb47060389 - 23 May 2025

Abstract

The pathogenesis of inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn’s disease, remains incompletely understood. Amomum villosum Lour. (Zingiberaceae) is a traditional herbal medicine used across Asia to treat digestive and inflammatory disorders. This study investigated the therapeutic effects of a [...] Read more.

The pathogenesis of inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn’s disease, remains incompletely understood. Amomum villosum Lour. (Zingiberaceae) is a traditional herbal medicine used across Asia to treat digestive and inflammatory disorders. This study investigated the therapeutic effects of a water extract derived from the fruits of AV (referred to as AVE) in a mouse model of colitis induced by dextran sulfate sodium (DSS). The protective effects of AVE were evaluated by monitoring changes in body weight and colon length, as well as histological and molecular markers of inflammation. Neutrophil infiltration and levels of inflammatory cytokines in colon tissue and serum were assessed, and the integrity of the intestinal epithelial barrier was examined via Western blot analysis. Treatment with AVE significantly alleviated DSS-induced colitis, as evidenced by improved body weight, longer colon length, and reduced inflammatory responses. AVE administration restored tight junction protein expression (zonula occludens-1 [ZO-1] and occludin), suppressed phosphorylation of mitogen-activated protein kinases—specifically, extracellular signal-regulated kinase (ERK) and p38—and inhibited the expression of inflammatory mediators including tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2), interleukin (IL)-6, IL-1β, and myeloperoxidase (MPO) activity. These findings suggest that oral AVE treatment effectively protects against experimental colitis by modulating inflammatory signaling and preserving epithelial barrier integrity. Further studies are warranted to explore the clinical potential and safety of AVE in the management of IBD. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Innovative Therapeutic Approaches in Inflammatory Diseases, Pioneering Precision Medicine Solutions)

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12 pages, 1581 KiB

Open AccessArticle

Anti-Inflammatory Effects of Caulerpa okamurae Extracts on Porphyromonas gingivalis-Stimulated RAW 264.7 Macrophages

by Chae-yun Lee, Min-jeong Kim and Hyun-jin Kim

Curr. Issues Mol. Biol. 2025, 47(6), 388; https://doi.org/10.3390/cimb47060388 - 23 May 2025

Abstract

Caulebra okamurae (C. okamurae), a green seaweed, has been reported to exhibit pharmacological properties, including anti-obesity and anti-diabetic effects. This study investigated the anti-inflammatory effects of C. okamurae extracts on periodontal health. The cell viability of RAW 264.7 macrophages was dose-dependently [...] Read more.

Caulebra okamurae (C. okamurae), a green seaweed, has been reported to exhibit pharmacological properties, including anti-obesity and anti-diabetic effects. This study investigated the anti-inflammatory effects of C. okamurae extracts on periodontal health. The cell viability of RAW 264.7 macrophages was dose-dependently assessed using an MTS assay. The anti-inflammatory activity of C. okamurae on Porphyromonas gingivalis (P. gingivalis)-stimulated RAW 264.7 macrophages was evaluated by measuring nitric oxide (NO) production. mRNA expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β were quantified via quantitative real-time PCR (qRT-PCR). The protein expression of iNOS, p-IKKα/β, p-IκBα, and NF-κB p65 was examined using Western blot and immunofluorescence. The results demonstrated that C. okamurae extracts exhibited no cytotoxicity in RAW 264.7 macrophages at concentrations of 0.2, 2, 20, and 200 μg/mL. The extracts dose-dependently reduced NO production, downregulated mRNA levels of proinflammatory cytokines, and inhibited iNOS expression in P. gingivalis-stimulated RAW 264.7 macrophages, a model commonly used to study periodontal inflammation. Furthermore, the extracts suppressed the phosphorylation of IKKα/β and IκBα and prevented the NF-κB p65 nuclear translocation. These findings suggest that C. okamurae extracts inhibit NF-κB signaling activation triggered by the periodontal pathogen, highlighting their potential anti-inflammatory effects, relevant to periodontal disease. Full article

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

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15 pages, 2203 KiB

Open AccessArticle

Pre- and Postnatal Fine Particulate Matter Exposure and Renal Fibrogenesis in Adult Male Rats: The Role of Vitamin D Supplementation

by Min-Hwa Son, Hyung-Eun Yim, Yu-Seon Lee, Yoon-Jeong Nam and Ju-Han Lee

Curr. Issues Mol. Biol. 2025, 47(6), 387; https://doi.org/10.3390/cimb47060387 - 22 May 2025

Abstract

Prolonged exposure to fine particulate matter (PM_2.5) has been implicated in accelerated aging, including organ fibrosis. This study aimed to investigate whether prenatal and postnatal PM_2.5 exposure promotes renal fibrogenesis in adulthood and whether long-term vitamin D supplementation alleviates associated [...] Read more.

Prolonged exposure to fine particulate matter (PM_2.5) has been implicated in accelerated aging, including organ fibrosis. This study aimed to investigate whether prenatal and postnatal PM_2.5 exposure promotes renal fibrogenesis in adulthood and whether long-term vitamin D supplementation alleviates associated renal injury. Pregnant Sprague-Dawley rats were randomly assigned to three groups: control (normal saline, NS), PM_2.5 exposure, and PM_2.5 exposure with vitamin D supplementation during gestation and lactation (n = 3/group). Male offspring were subsequently exposed to the same conditions from postnatal weeks 3 to 8 (n = 7/group). On postnatal day 56, PM_2.5-exposed rats showed lower body weight and more severe glomerular and tubulointerstitial damage compared to controls. Serum calcium levels were elevated in the PM_2.5 group. The expression of intrarenal renin, transforming growth factor-β1, α-smooth muscle actin, and vimentin was upregulated, accompanied by increased collagen deposition. Long-term vitamin D supplementation reversed most of these changes, except for intrarenal vimentin expression and serum calcium levels. These findings indicate that prenatal and postnatal PM_2.5 exposure can activate intrarenal renin signaling and fibrogenic pathways, contributing to renal fibrosis later in life. Long-term vitamin D supplementation may provide partial protective effects against PM_2.5-induced renal fibrogenesis. Full article

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

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17 pages, 2112 KiB

Open AccessArticle

Mitigation of 3.5 GHz Electromagnetic Field-Induced BV2 Microglial Cytotoxicity by Polydeoxyribonucleotide

by Shailashree Pachhapure, Amila Mufida, Qun Wei, Jong-Soon Choi and Byeong-Churl Jang

Curr. Issues Mol. Biol. 2025, 47(6), 386; https://doi.org/10.3390/cimb47060386 - 22 May 2025

Abstract

Emerging evidence highlights the biological risks associated with electromagnetic fields (EMFs) generated by electronic devices. The toxic effects and mechanisms induced by exposure to EMFs on microglial cells and natural substances that inhibit them are limited to date. Here, we investigated whether exposure [...] Read more.

Emerging evidence highlights the biological risks associated with electromagnetic fields (EMFs) generated by electronic devices. The toxic effects and mechanisms induced by exposure to EMFs on microglial cells and natural substances that inhibit them are limited to date. Here, we investigated whether exposure to 3.5 GHz EMF radiation, potentially generated by smartphones working in 5G communication or cooking using microwave ovens, affects the growth of BV2 mouse microglial cells and polydeoxyribonucleotide (PDRN), a DNA preparation derived from salmon sperm, inhibits it. Of note, exposure to 3.5 GHz EMF radiation for 2 h markedly inhibited the growth and triggered apoptosis in BV2 cells, characterized by the reduced number of surviving cells, increased genomic DNA fragmentation, increased reactive oxygen species (ROS) levels, and altered phosphorylation and expression levels of JNK-1/2, p38 MAPK, ERK-1/2, eIF-2α, and procaspase-9. Pharmacological inhibition studies revealed that JNK-1/2 and p38 MAPK activation and ROS generation were crucial for 3.5 GHz EMF-induced BV2 cytotoxicity. Of interest, PDRN effectively countered these effects by inhibiting the activation of JNK-1/2, p38 MAPK, and caspase-9, and the production of ROS, although it did not affect eIF-2 phosphorylation. In conclusion, this study is the first to report that PDRN protects against 3.5 GHz EMF-induced toxicities in BV2 microglial cells, and PDRN’s protective effects on 3.5 GHz EMF-induced BV2 cytotoxicity are mediated primarily by modulating ROS, JNK-1/2, p38 MAPK, and caspase-9. Full article

(This article belongs to the Special Issue Radiation-Induced Cellular and Molecular Responses)

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16 pages, 4237 KiB

Open AccessArticle

Bioinformatics Analysis of Candidate Genes Related to Fat Deposition in Yaks at Different Energy Levels

by Boxuan Yang, Xiaolin Luo, Xiangfei Zhang, Tianwu An, Qin Bai, Quan Sha and Hongwen Zhao

Curr. Issues Mol. Biol. 2025, 47(6), 385; https://doi.org/10.3390/cimb47060385 - 22 May 2025

Abstract

Fat deposition is important for the growth and reproduction of yaks. To investigate the differentially expressed genes in muscle tissue and fat deposition in yaks at varying energy levels, 12 healthy adult yaks with similar body conditions were selected as research subjects. They [...] Read more.

Fat deposition is important for the growth and reproduction of yaks. To investigate the differentially expressed genes in muscle tissue and fat deposition in yaks at varying energy levels, 12 healthy adult yaks with similar body conditions were selected as research subjects. They were slaughtered after being reared at the following three different energy levels: low (L), medium (M), and high (H). The most extensive dorsal muscles were collected and screened for fat metabolism-related genes using Illumina for transcriptome sequencing. The results of transcriptome analysis showed that a total of 1430 differentially expressed genes were identified across the three groups of samples. Among these, 281 differentially expressed genes were identified between the high-energy group and the low-energy group; 365 differentially expressed genes were identified between the low-energy group and the medium-energy group; and 784 differentially expressed genes were identified between the medium-energy group and the high-energy group. GO and KEGG annotations indicated that across the three different energy levels the main enriched genes were found in the adipose cytokine signaling pathways, including, AMPK, the MAPK signaling pathway, and the PI3K-Akt signaling pathway. Both up- and down-regulation of FGF-10 and NR4A1 expression were found in fat deposition-related candidate genes; the seven up-regulated genes were FGF-10, ACACB, DUSP1, c-FOS, NR4A1, RGS2, and FOXO1, and the ten down-regulated genes were LDLR, IRS2, FGF (FGF-10), TRAF2, NR4A1, HSPB1, SGK1, MYL3, LEPR, and SLC2A1. Two of the most common fat deposition genes, FASN and PDK4, were selected for q-PCR validation, along with ten candidate genes obtained from the transcriptome screening. The results showed that the expression trends of 12 genes in the three different energy level groups were consistent with those from transcriptome sequencing. This study revealed the complex transcriptome profiles of fat deposition in the muscle tissues of yaks at varying energy feeding levels and uncovered candidate genes involved in fat deposition. Full article

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

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17 pages, 3712 KiB

Open AccessArticle

Genome-Wide Detection of Leukemia Biomarkers from lincRNA–Protein-Coding Gene Interaction Networks in the Three-Dimensional Chromatin Structure

by Yue Hou, Wei Ning, Muren Huhe and Chuanjun Shu

Curr. Issues Mol. Biol. 2025, 47(6), 384; https://doi.org/10.3390/cimb47060384 - 22 May 2025

Abstract

The human genome is widely transcribed, with part of these transcribed regions producing stably expressed protein-coding or non-coding RNAs. Long intergenic non-coding RNAs (lincRNAs) are significantly differentially expressed in various cell lines and tissues. However, the influence of their transcription events remains unclear. [...] Read more.

The human genome is widely transcribed, with part of these transcribed regions producing stably expressed protein-coding or non-coding RNAs. Long intergenic non-coding RNAs (lincRNAs) are significantly differentially expressed in various cell lines and tissues. However, the influence of their transcription events remains unclear. In this study, we constructed a human genomic interaction network and found frequent interactions between lincRNA genes and protein-coding genes that are highly related to the occupancy of RNA polymerase II on the lincRNA gene. Interestingly, in the human genome interaction networks, the degree of lincRNA genes was significantly higher than that of protein-coding genes. The promoter regions of the protein-coding genes interacting with the lincRNA genes are enriched with R-loop structures, indicating that lincRNA may influence the target genes through R-loop structures. These promoters were enriched in more transcription factor binding sites. Furthermore, the whole network and sub-network could be utilized to explore potential biomarkers of leukemia. We found that zinc finger protein 668 (ZNF668), eosinophil granule ontogeny transcript (EGOT), and glutamate metabotropic receptor 7 (GRM7) could serve as novel biomarkers for acute myeloid leukemia (LMAL). Pasireotide acetate (CAS No. 396091-76-2) represents a potential drug for LMAL patients. These results suggested that potential biomarkers and corresponding drugs for cancer could be identified based on lincRNA–promoter network/sub-network topological parameters. Full article

(This article belongs to the Special Issue The Contribution and Application of Molecular Biology in the Applied Biosciences—Focusing on Medicine, Biomaterials and Tissue Engineering Fields, 2nd Edition)

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19 pages, 635 KiB

Open AccessReview

Relevance of Glucagon-Like Peptide 1 (GLP-1) in Inflammatory Bowel Diseases: A Narrative Review

by Antonietta Gerarda Gravina, Raffaele Pellegrino, Michele Izzo, Ilaria De Costanzo, Giuseppe Imperio, Fabio Landa, Assunta Tambaro and Alessandro Federico

Curr. Issues Mol. Biol. 2025, 47(5), 383; https://doi.org/10.3390/cimb47050383 - 21 May 2025

Abstract

Inflammatory bowel diseases (IBDs) are complex immune-mediated disorders characterised by an unpredictable direction and commonly associated metabolic comorbidities along with obesity and type 2 diabetes mellitus (T2DM). Recent evidence has highlighted the therapeutic capacity of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), already [...] Read more.

Inflammatory bowel diseases (IBDs) are complex immune-mediated disorders characterised by an unpredictable direction and commonly associated metabolic comorbidities along with obesity and type 2 diabetes mellitus (T2DM). Recent evidence has highlighted the therapeutic capacity of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), already employed in treating T2DM and obesity, in modulating systemic and intestinal inflammatory responses. This narrative review examines the general organic traits of GLP-1, with a specific awareness of its primary gastrointestinal actions and the efficacy of GLP-1 RAs in promoting weight loss and dealing with glycaemic control, mainly in sufferers with IBD. Furthermore, the effects of those agonists on the progression of IBD, their protection profile, their impact on bowel preparation for endoscopic procedures, and their therapeutic capacity, supported through preclinical and early clinical studies, are discussed. GLP-1 RAs appear to lessen the intestinal inflammatory burden by enhancing intestinal epithelial barrier features and modulating the gut microbiota. However, further clinical research will be necessary to verify whether GLP-1 RAs could play a position in IBD treatment. Full article

(This article belongs to the Special Issue Intestinal Inflammation: From Molecular Mechanisms to Therapeutic Strategies)

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22 pages, 5296 KiB

Open AccessReview

The Role of Mitochondrial Energy Metabolism in the Mechanism of Exercise Improving Depression

by Yuwei Liu, Chenghao Zhong, Yuxin Yang, Jianbo Hu, Xiaoyan Yi, Jiating Huang, Haonan Li, Xiaojie Liu, Ke Xue and Xianghe Chen

Curr. Issues Mol. Biol. 2025, 47(5), 382; https://doi.org/10.3390/cimb47050382 - 21 May 2025

Abstract

Depression is the most disabling neuropsychiatric disorder, but its exact mechanisms remain unclear. Mitochondrial energy metabolism may play a key role in the onset and development of depression. Cytokines such as PGC-1α, NLRP3, and BDNF can influence mitochondrial energy metabolism by regulating mitochondrial [...] Read more.

Depression is the most disabling neuropsychiatric disorder, but its exact mechanisms remain unclear. Mitochondrial energy metabolism may play a key role in the onset and development of depression. Cytokines such as PGC-1α, NLRP3, and BDNF can influence mitochondrial energy metabolism by regulating mitochondrial biogenesis, immune inflammation, and neuroplasticity, thereby mediating the occurrence and progression of depression. Exercise can improve depression by regulating mitochondrial energy metabolism. The molecular mechanisms are closely related to the upregulation of exercise-induced PGC-1α, AMPK, SIRT1, and BDNF expression, as well as the downregulation of NLRP3 expression. These factors can activate key factors or pathways such as Nrf2, AMPK, and PKA/CREB, while inhibiting the excessive activation of NF-κB. Through these mechanisms, they regulate the expression of downstream target genes (such as TFAM, NRF1, CREB, and Bcl-2), thereby enhancing mitochondrial biogenesis and improving the quantity and quality of mitochondria. Additionally, they can act to inhibit the release of inflammatory factors to improve immune inflammation, enhance neuroplasticity, promote neuronal growth, and facilitate synapse formation and remodeling, thereby enhancing mitochondrial energy metabolism and improving its dysfunction, which in turn alleviates depression. Currently, there is a lack of systematic and comprehensive research on the mechanisms by which exercise improves depression through mitochondrial energy metabolism. Therefore, this article aims to review and analyze the role of mitochondrial energy metabolism in the improvement of depression through exercise, in order to provide a new theoretical basis and research ideas for the prevention and treatment of depression. Full article

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

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17 pages, 313 KiB

Open AccessReview

The Struggle Between Chimeric Antigen Receptor T-Cell Therapy and Neurological Complications in Acute Lymphoblastic Leukemia Treatment

by Norwin Kubick, Marzena Łazarczyk, Omar Awad, Michał Ławiński, Jarosław Olav Horbańczuk, Mariusz Sacharczuk, Atanas G. Atanasov, Piotr Religa and Michel Edwar Mickael

Curr. Issues Mol. Biol. 2025, 47(5), 381; https://doi.org/10.3390/cimb47050381 - 21 May 2025

Abstract

Acute lymphoblastic leukemia (ALL) accounts for approximately 25% of childhood cancers and 20% of leukemia cases in adults, with a higher prevalence in males than females. It is characterized by symptoms such as fatigue, fever, and bone pain and poses a significant risk [...] Read more.

Acute lymphoblastic leukemia (ALL) accounts for approximately 25% of childhood cancers and 20% of leukemia cases in adults, with a higher prevalence in males than females. It is characterized by symptoms such as fatigue, fever, and bone pain and poses a significant risk of mortality if left untreated. While chemotherapy and stem cell transplantation are standard treatments, their efficacy declines in relapsed or refractory cases, highlighting the need for innovative therapeutic approaches. CAR T-cell therapy has emerged as a transformative technology, offering the potential to overcome these challenges and deliver durable remissions. CAR T-cell therapy demonstrates significant advantages, including targeting specific antigens, overcoming high-risk genetic mutations, and achieving sustained remissions in both pediatric and adult patients. However, notable challenges remain, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). In this review, we focus on neurological symptoms associated with CAR T-cell therapy in treating ALL and discuss current and future strategies aiming at reducing their risk. Full article

(This article belongs to the Special Issue Novel Immunotherapy for Neurological Diseases)

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