Current Issues in Molecular Biology

16 pages, 687 KiB

Open AccessArticle

Differential Profiles of Gut Microbiota-Derived Metabolites of Bile Acids and Propionate as Potential Predictors of Depressive Disorder in Women with Morbid Obesity at High Risk of Metabolic Dysfunction-Associated Steatotic Liver Disease—A Pilot Study

by Joanna Michalina Jurek, Belen Xifré, Elena Cristina Rusu, Helena Clavero-Mestres, Razieh Mahmoudian, Carmen Aguilar, David Riesco, Javier Ugarte Chicote, Salomé Martinez, Marga Vives, Fàtima Sabench and Teresa Auguet

Curr. Issues Mol. Biol. 2025, 47(5), 353; https://doi.org/10.3390/cimb47050353 (registering DOI) - 12 May 2025

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a liver condition linked to cardiometabolic diseases and mental health issues, with studies highlighting disruptions in gut microbiota activity, including bile acid (BA) metabolism. Therefore, the main aim of this exploratory analysis was to assess microbiota-derived [...] Read more.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a liver condition linked to cardiometabolic diseases and mental health issues, with studies highlighting disruptions in gut microbiota activity, including bile acid (BA) metabolism. Therefore, the main aim of this exploratory analysis was to assess microbiota-derived metabolites, specifically BAs and short-chain fatty acids (SCFAs), as potential biomarkers of depressive disorder (DD) in women with morbid obesity at MASLD risk. In this pilot study, 33 females with morbid obesity who were scheduled for bariatric surgery were evaluated. Medical and clinical data were collected, and microbial metabolites from pre-surgery blood samples were analyzed. Patients were stratified according to the presence of DD. Analysis with Spearman’s rank test was used to assess correlations and logistic regression models were built to evaluate biomarkers as predictors of DD risk using both receiver operating characteristic (ROC) and precision–recall curves. In this cohort, 30.3% of females were reported to have DD, in addition to significantly elevated levels of certain BAs and SCFAs, including glycodeoxycholic acid (GDCA) and propionate, which were also correlated with some metabolic biomarkers. However, there were no differences in the incidence of MASLD or metabolic syndrome between patients with DD or without. In conclusion, microbiota-derived metabolites such as GDCA and propionate may influence DD risk in females with morbid obesity; however, their potential use as predictive biomarkers should be further investigated to confirm their role in psycho-metabolic conditions. Full article

(This article belongs to the Special Issue Molecular Mechanisms Underlying Fatty Liver Disease: From Pathogenesis to Treatment, 2nd Edition)

45 pages, 15230 KiB

Open AccessArticle

The Transcription Axes ERK-Elk1, JNK-cJun, and JAK-STAT Promote Autophagy Activation and Proteasome Inhibitor Resistance in Prostate Cancer Cells

by Georgios Kalampounias, Kalliopi Zafeiropoulou, Theodosia Androutsopoulou, Spyridon Alexis, Argiris Symeonidis and Panagiotis Katsoris

Curr. Issues Mol. Biol. 2025, 47(5), 352; https://doi.org/10.3390/cimb47050352 - 12 May 2025

Abstract

The rapid emergence of resistance limits the application of proteasome inhibitors against solid tumors, despite their effectiveness in the treatment of hematological malignancies. Resistant phenotypes are complex and multifaceted, and, thus, the mechanisms involved have not been adequately described. In this study, a [...] Read more.

The rapid emergence of resistance limits the application of proteasome inhibitors against solid tumors, despite their effectiveness in the treatment of hematological malignancies. Resistant phenotypes are complex and multifaceted, and, thus, the mechanisms involved have not been adequately described. In this study, a Bortezomib-resistant prostate cancer cell line is created by using the PC-3 cell as a prostate carcinoma model of high metastatic potential. The main biochemical differences and adaptations exhibited by the resistant cells revolve around apoptosis evasion, autophagy induction (functioning as a ubiquitin-proteasome system substitute), expression of epithelial-to-mesenchymal transition markers, and increased aggressiveness. Broad-spectrum signaling pathway analyses also reveal an upregulation and activation of Nf-κB, STAT3, cJun, and Elk1 transcription factors in the resistant cells. Additionally, intracellular reactive oxygen species assays reveal a downregulation in resistant cells, which is theorized to be a consequence of metabolic changes, increased autophagic flux, and antioxidative enzyme action. These findings expand our understanding of proteasome inhibitor resistance and highlight key kinases and transcription factors as novel potential therapeutic targets. Effective inhibition of resistance-specific pathways could re-sensitize the cells to proteasome inhibitors, thus surpassing current therapeutic limitations. Full article

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

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7 pages, 585 KiB

Open AccessBrief Report

The Superoxide Dismutase Family in Balloon Flower (Platycodon grandiflorus): Phylogenetic Relationships, Structural Characteristics, and Expression Patterns

by Tae Kyung Hyun

Curr. Issues Mol. Biol. 2025, 47(5), 351; https://doi.org/10.3390/cimb47050351 - 12 May 2025

Abstract

Superoxide dismutases (SODs) are essential antioxidant enzymes that protect plant cells from oxidative stress, thereby preserving cellular integrity. This study presents a comprehensive genome-wide analysis of the SOD gene family in Platycodon grandiflorus, identifying seven genes classified into three distinct groups based [...] Read more.

Superoxide dismutases (SODs) are essential antioxidant enzymes that protect plant cells from oxidative stress, thereby preserving cellular integrity. This study presents a comprehensive genome-wide analysis of the SOD gene family in Platycodon grandiflorus, identifying seven genes classified into three distinct groups based on phylogenetic relationships. Detailed bioinformatics analyses revealed variations in structural characteristics and physicochemical properties. PlgSODs were predicted to localize primarily to the chloroplast and mitochondria. Tissue-specific expression patterns indicate that PlgSOD genes play important roles in plant growth and development. Furthermore, promoter analysis identified several potential transcription factors (TFs), including members of the B3, Dof, and MYB-related families, which are known for their involvement in stress responses. These TFs are likely to regulate multiple PlgSOD genes, suggesting a coordinated transcriptional regulation mechanism under specific physiological or stress conditions. Taken together, these findings provide valuable insights into the functional roles of SODs in P. grandiflorus and lay the groundwork for future genetic and biotechnological strategies aimed at enhancing stress tolerance in this species. Full article

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

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16 pages, 1159 KiB

Open AccessReview

Decoding Quantitative Traits in Yaks: Genomic Insights for Improved Breeding Strategies

by Yujiao Fu, Yuanyuan Yu, Xinjia Yan, Daoliang Lan and Jiabo Wang

Curr. Issues Mol. Biol. 2025, 47(5), 350; https://doi.org/10.3390/cimb47050350 - 12 May 2025

Abstract

The yak (Bos grunniens), the only large domesticated species endemic to the Qinghai–Tibet Plateau, is a vital resource for local livelihoods and regional economic sustainability. However, yak breeding faces significant challenges, including limited understanding of the genetic architecture underlying quantitative traits, [...] Read more.

The yak (Bos grunniens), the only large domesticated species endemic to the Qinghai–Tibet Plateau, is a vital resource for local livelihoods and regional economic sustainability. However, yak breeding faces significant challenges, including limited understanding of the genetic architecture underlying quantitative traits, inadequate advanced breeding strategies, and the sterility of hybrid offspring from yak–cattle crosses. These constraints have hindered genetic progress in key production traits. To address these issues, integrating modern genomic tools into yak breeding programs is imperative. This review explores the application and potential of molecular marker-assisted selection (MAS) and genomic prediction (GP) in yak genetic improvement. We systematically evaluate critical components of genomic breeding pipelines, including: (1) phenotypic trait assessment, (2) sample collection strategies, (3) reference population design, (4) high-throughput genotyping (via genome sequencing and SNP arrays), (5) predictive model development, and (6) heritability estimation. By synthesizing current advances and methodologies, this work aims to provide a framework for leveraging genomic technologies to enhance breeding efficiency, preserve genetic diversity, and accelerate genetic gains in yak populations. Full article

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

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11 pages, 3901 KiB

Open AccessArticle

A Novel Mutation in the Androgen Receptor Gene of Female Patients with 46,XY Karyotype

by Inayet Nur Uslu, Nuriye Gokce, Gulsevinc Aksoy, Nihal Inandiklioglu, Bilgin Yuksel, Munis Dundar and Osman Demirhan

Curr. Issues Mol. Biol. 2025, 47(5), 349; https://doi.org/10.3390/cimb47050349 - 10 May 2025

Viewed by 98

Abstract

Background: In this study, we aimed to analyze androgen receptor (AR) gene mutations in five members of a family with complete androgen insensitivity syndrome (CAIS). Methods: Peripheral blood samples were collected from the proband and four relatives (mother, sister, and two [...] Read more.

Background: In this study, we aimed to analyze androgen receptor (AR) gene mutations in five members of a family with complete androgen insensitivity syndrome (CAIS). Methods: Peripheral blood samples were collected from the proband and four relatives (mother, sister, and two aunts). Cytogenetic imaging and chromosomal analysis were per-formed to elucidate the genetic basis of the condition. Clinical Exome Sequencing (CES) was conducted to identify candidate variants, which were subsequently validated using Sanger sequencing. Evolutionary conservation analysis was performed for the identified AR gene mutation. Results: Our analyses revealed that the proband, sister, Aunt I, and Aunt II exhibited a 46,XY karyotype and carried the SRY gene. The mother, however, had a 46,XX karyotype, and did not carry the SRY gene, confirming X-linked recessive inheritance of the condition. CES results demonstrated that the proband, sister, Aunt I, and Aunt II harbored a hemizygous c.2246C>T (p.Ala749Val) mutation, while the mother carried this mutation in a heterozygous state. The presence of this mutation was confirmed by Sanger sequencing. Evolutionary conservation analysis indicated that the mutation is conserved among vertebrates. Conclusion: in conclusion, we identified a novel missense mutation (c.2246C>T) in the AR gene in five members of a CAIS-affected family, which has not been previously reported in the literature. Full article

(This article belongs to the Collection Feature Papers in Molecular Medicine 2025)

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18 pages, 663 KiB

Open AccessArticle

lncRNAs as Biomarkers of Hepatocellular Carcinoma Risk and Liver Damage in Advanced Chronic Hepatitis C

by Driéle B. dos Santos, Geysson J. Fernandez, Letícia T. Silva, Giovanni F. Silva, Estela O. Lima, Aline F. Galvani, Guilherme L. Pereira and Adriana C. Ferrasi

Curr. Issues Mol. Biol. 2025, 47(5), 348; https://doi.org/10.3390/cimb47050348 - 10 May 2025

Viewed by 106

Abstract

Background/Objectives: LncRNAs have emerged as promising biomarkers due to their role in gene regulation of carcinogenesis and presence in biological fluids. Liquid biopsies offer a less invasive alternative to tissue biopsies, improving early cancer diagnosis and surveillance. Hepatocellular carcinoma (HCC) is among the [...] Read more.

Background/Objectives: LncRNAs have emerged as promising biomarkers due to their role in gene regulation of carcinogenesis and presence in biological fluids. Liquid biopsies offer a less invasive alternative to tissue biopsies, improving early cancer diagnosis and surveillance. Hepatocellular carcinoma (HCC) is among the most lethal and prevalent cancers. Late diagnoses contribute to poor prognosis, particularly in chronic hepatitis C (CHC) patients, which is a major risk factor for HCC. Tissue biopsies for HCC diagnosis pose risks, including tumor dissemination, highlighting the urgent need for noninvasive biomarkers. Several lncRNAs are deregulated in HCC and may be potential markers for assessing HCC risk in CHC. This study evaluated seven lncRNAs as plasma biomarkers for HCC risk in CHC. Methods: lncRNA expression was analyzed by RT-qPCR in three groups: CHC patients who developed HCC within a 5-year follow-up (HCCpos), CHC patients who did not develop HCC within a 5-year follow-up (HCCneg), and healthy blood donors (CG). Results: This study found that plasma lncRNAs HULC and RP11-731F5.2 are potential biomarkers for HCC risk, while RP11-731F5.2 and KCNQ1OT1 may serve as noninvasive biomarkers for liver damage due to HCV infection. Conclusions: These findings highlight the potential of lncRNAs in enhancing early diagnosis and monitoring of HCC in CHC patients. Full article

(This article belongs to the Special Issue Molecular Functions of Long Non-Coding RNAs: Implications for Diseases and Therapy)

23 pages, 1318 KiB

Open AccessReview

Emerging Tumor Biomarkers in Pancreatic Cancer and Their Clinical Implications

by Dimitrios Stefanoudakis, Maximos Frountzas, Nikolaos V. Michalopoulos, Dimitrios Schizas, Dimitrios Theodorou and Konstantinos G. Toutouzas

Curr. Issues Mol. Biol. 2025, 47(5), 347; https://doi.org/10.3390/cimb47050347 - 10 May 2025

Viewed by 63

Abstract

Pancreatic cancer is one of the deadliest malignancies, and this is attributed to the fact that it is diagnosed at a late stage and there are limited treatment options. Tumor biomarkers are used to improve early diagnosis, treatment, and decision-making and to estimate [...] Read more.

Pancreatic cancer is one of the deadliest malignancies, and this is attributed to the fact that it is diagnosed at a late stage and there are limited treatment options. Tumor biomarkers are used to improve early diagnosis, treatment, and decision-making and to estimate patients’ outcomes. This review aims to discuss the new functions of important biomarkers, such as miRNAs, GATA6, L1CAM, and MUC1 in pancreatic cancer. MiRNAs, including miR-21, miR-155, and miR-196a, are prognostic in PC and may be potential therapeutic targets through the regulation of oncogenic pathways and chemoresistance. GATA6, a transcription factor that controls tumor differentiation and immune escape, has been proposed as a pancreatic ductal adenocarcinoma (PDAC) subtyping marker and a predictor of chemotherapy response. L1CAM promotes tumor growth, invasion, and immune suppression, which leads to the formation of new metastases and perineural invasion. MUC1, a glycoprotein with altered glycosylation, is a marker of tumor progression, immune escape, and resistance to chemotherapy. These biomarkers can be combined into diagnostic panels that may increase the accuracy of the diagnosis and help to individualize the treatment plan. However, the present study is inconclusive, and more clinical evidence is needed to apply these biomarkers in clinical practice. More specific research should be directed towards the development of new targeted therapies that would act on these molecular targets and improve the prognosis and treatment of pancreatic cancer. Full article

(This article belongs to the Section Molecular Medicine)

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11 pages, 1418 KiB

Open AccessArticle

The Role of BCL-2 Expression in Patients with Myelodysplastic Neoplasms

by Bartłomiej Kuszczak, Krzysztof Zduniak, Angela Jendzierowska, Tomasz Wróbel, Piotr Ziółkowski and Justyna Rybka

Curr. Issues Mol. Biol. 2025, 47(5), 346; https://doi.org/10.3390/cimb47050346 - 10 May 2025

Viewed by 52

Abstract

Myelodysplastic neoplasms (MDS) represent a heterogeneous group of neoplastic bone marrow disorders. A crucial component in regulating bone marrow cell apoptosis is the B-cell CLL/lymphoma 2 (BCL-2) protein. This retrospective study aimed to assess BCL-2 expression by immunohistochemistry in trephine biopsy specimens from [...] Read more.

Myelodysplastic neoplasms (MDS) represent a heterogeneous group of neoplastic bone marrow disorders. A crucial component in regulating bone marrow cell apoptosis is the B-cell CLL/lymphoma 2 (BCL-2) protein. This retrospective study aimed to assess BCL-2 expression by immunohistochemistry in trephine biopsy specimens from 76 patients diagnosed with MDS. The obtained retrospective results were correlated with clinical parameters, including age, sex, MDS subtype, IPSS, IPSS-R, bone marrow blast percentage, Ogata score, response to treatment, blood morphology parameters, and overall survival (OS). The median follow-up duration was 16 months. During the observation period, 58 patients died (median OS of this group: 14.6 months), and 25 patients experienced progression to acute myeloid leukemia. The median BCL-2 expression assessed using the Histoscore (H-score) was 10. Patients with BCL-2 expression below 10 had better survival outcomes than those with expression ≥ 10. Furthermore, patients without detectable BCL-2 expression had significantly better survival compared to those with detectable BCL-2 expression (p = 0.0084). Higher BCL-2 expression was significantly associated with high and very high cytogenetic risk, as defined by IPSS-R. BCL-2 immunohistochemistry should be viewed as a complementary biomarker that, when integrated with IPSS-R and mutational data, could refine therapeutic algorithms. Full article

(This article belongs to the Special Issue Targeting Tumor Microenvironment for Cancer Therapy, 3rd Edition)

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18 pages, 2484 KiB

Open AccessArticle

The N-Linked Glycosylation Site N201 in eel Lutropin/Choriogonadotropin Receptor Is Uniquely Indispensable for cAMP Responsiveness and Receptor Surface Loss, but Not pERK1/2 Activity

by Munkhzaya Byambaragchaa, Dong-Wan Kim, Sei Hyen Park, Myung-Hwa Kang and Kwan-Sik Min

Curr. Issues Mol. Biol. 2025, 47(5), 345; https://doi.org/10.3390/cimb47050345 - 9 May 2025

Viewed by 159

Abstract

The seven transmembrane-spanning lutropin/chorionic gonadotropin receptors (LH/CGRs) trigger extracellular signal-related kinases (ERK1/2) via a noticeable network dependent on either G protein (Gαs) or β-arrestins. LH/CGRs are highly conserved, with the largest region within the transmembrane helices and common N-glycosylation sites in the extracellular [...] Read more.

The seven transmembrane-spanning lutropin/chorionic gonadotropin receptors (LH/CGRs) trigger extracellular signal-related kinases (ERK1/2) via a noticeable network dependent on either G protein (Gαs) or β-arrestins. LH/CGRs are highly conserved, with the largest region within the transmembrane helices and common N-glycosylation sites in the extracellular domain. We aimed to determine the glycosylation sites that play crucial roles in cAMP and pERK1/2 regulation by constructing four mutants (N49Q, N201Q, N306Q, and N312Q). The cAMP response in cells expressing the N201Q mutant was completely impaired, despite high-dose agonist treatment. The cell-surface expression level was lowest in transiently transfected cells, but normal surface loss of the receptor occurred in cells expressing the wild-type and other mutant proteins. However, the N201Q mutant was only slightly reduced after 5 min of agonist stimulation. All mutants showed a peak in cAMP signaling 5 min after stimulation with a pERK1/2 agonist. Of note, cAMP activity was completely impaired in the N201Q mutant; however, this mutant still displayed a pERK1/2 response. These data show that the specific N-linked glycosylation site in eel LH/CGR is clearly distinguished by its differential responsiveness to cAMP signaling and pERK1/2 activity. Thus, we suggest that the cAMP and pERK1/2 signaling pathways involving eel LH/CGRs represent pleiotropic signal transduction induced by agonist treatment. Full article

(This article belongs to the Special Issue Hormonal Regulation in Germ Cell Development)

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30 pages, 3926 KiB

Open AccessReview

Balancing Microglial Density and Activation in Central Nervous System Development and Disease

by Shunqi Wang, Liangjing Pan, Chong Sun, Chaolin Ma and Haili Pan

Curr. Issues Mol. Biol. 2025, 47(5), 344; https://doi.org/10.3390/cimb47050344 - 9 May 2025

Viewed by 120

Abstract

Microglia, the resident immune cells of the central nervous system, play multifaceted roles in both health and disease. During development, they regulate neurogenesis and refine neural circuits through synaptic pruning. In adulthood, microglia maintain homeostasis and dynamically respond to pathological insults, where they [...] Read more.

Microglia, the resident immune cells of the central nervous system, play multifaceted roles in both health and disease. During development, they regulate neurogenesis and refine neural circuits through synaptic pruning. In adulthood, microglia maintain homeostasis and dynamically respond to pathological insults, where they contribute to responding to neuroinflammatory challenges. This review summarizes microglial contributions to neurodevelopment and also outlines their function across various neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis, highlighting both protective and detrimental effects. Finally, recent advances in microglial-targeted therapies and lifestyle-based interventions are highlighted, underscoring the translational potential of modulating microglial states. Elucidating the dual roles of microglia in development and disease could guide the design of therapeutic strategies aimed at enhancing neuroprotection while minimizing neurotoxicity. Full article

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

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21 pages, 2111 KiB

Open AccessReview

Key Roles of Brown, Subcutaneous, and Visceral Adipose Tissues in Obesity and Insulin Resistance

by Maria-Zinaida Dobre, Bogdana Virgolici and Olivia Timnea

Curr. Issues Mol. Biol. 2025, 47(5), 343; https://doi.org/10.3390/cimb47050343 - 9 May 2025

Viewed by 124

Abstract

Adipose tissue is a dynamic and heterogeneous organ with distinct depots that play divergent roles in metabolic regulation. This review highlights the functional differences between brown, subcutaneous, and visceral adipose tissue, and their contributions to obesity-related insulin resistance. We explore how chronic low-grade [...] Read more.

Adipose tissue is a dynamic and heterogeneous organ with distinct depots that play divergent roles in metabolic regulation. This review highlights the functional differences between brown, subcutaneous, and visceral adipose tissue, and their contributions to obesity-related insulin resistance. We explore how chronic low-grade inflammation, mitochondrial dysfunction, and fibrosis evolve within specific fat depots and how these changes disrupt systemic energy homeostasis. Visceral white adipose tissue (vWAT) emerges as a critical site of inflammation and metabolic inflexibility, while subcutaneous white adipose tissue (sWAT) may retain protective features in early obesity. The endocrine roles of adipokines and batokines are also discussed, emphasizing depot-specific signaling and systemic effects. Furthermore, we examine emerging therapeutic strategies aimed at modulating immune responses, enhancing mitochondrial function, and reprogramming adipose progenitor cells (APCs) to restore healthy tissue remodeling. A deeper understanding of adipose-depot-specific biology and progenitor cell dynamics offers promising avenues for personalized interventions in metabolic diseases. Full article

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

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15 pages, 4488 KiB

Open AccessArticle

Exploration of the Mechanisms of Acorus tatarinowii in the Treatment of Major Depressive Disorder Based on Network Pharmacology and Molecular Docking Techniques

by Li Han, Siwen Wei, Rong Wang, Yiran Liu, Yi Zhong and Huaiqing Luo

Curr. Issues Mol. Biol. 2025, 47(5), 342; https://doi.org/10.3390/cimb47050342 - 9 May 2025

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Abstract

Objective: To elucidate the molecular targets and mechanisms by which Acorus tatarinowii exerts therapeutic effects in major depressive disorder (MDD) using network pharmacology and molecular docking approaches. Methods: Bioactive compounds of Acorus tatarinowii were identified from comprehensive pharmacological databases. MDD-related targets were sourced [...] Read more.

Objective: To elucidate the molecular targets and mechanisms by which Acorus tatarinowii exerts therapeutic effects in major depressive disorder (MDD) using network pharmacology and molecular docking approaches. Methods: Bioactive compounds of Acorus tatarinowii were identified from comprehensive pharmacological databases. MDD-related targets were sourced from extensive genomic repositories. Overlapping targets were determined and subjected to network topology and protein–protein interaction (PPI) analyses to identify core targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to reveal pertinent biological processes and signaling pathways. Molecular docking simulations validated the interactions between key bioactive compounds and core targets. Results: A total of 57 bioactive compounds were identified in Acorus tatarinowii, including apigenin, heterotropan, and isoelemicin. Integrative analysis revealed 700 compound-related targets and 2590 MDD-associated targets, with 150 intersecting targets. Network analyses pinpointed five core targets: TP53, STAT3, AKT1, PIK3CA, and PIK3R1. GO enrichment identified 858 significant biological processes, while KEGG pathway analysis highlighted 155 enriched pathways, notably the PI3K-Akt, cAMP, and MAPK signaling pathways. Molecular docking studies demonstrated strong binding affinities between key compounds and their respective targets. Conclusions: This study delineates the multifaceted polypharmacological mechanisms through which Acorus tatarinowii may confer protective effects against major depressive disorder, underscoring its potential as a promising therapeutic agent. Full article

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

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15 pages, 3306 KiB

Open AccessArticle

Multidimensional Transcriptomics Reveals the Key Genes and Pathways Regulating the Acidity of Apples

by Wenyuan Yang, Hang Yu, Lian Tao and Hongjiang Xie

Curr. Issues Mol. Biol. 2025, 47(5), 341; https://doi.org/10.3390/cimb47050341 - 8 May 2025

Viewed by 191

Abstract

Low-acid apples are popular among consumers, but the mechanisms behind the complex differences in acidity among varieties that are caused by high altitude are not clear. In this study, we used the ‘Golden Delicious’ apple and its superior variant in the Western Sichuan [...] Read more.

Low-acid apples are popular among consumers, but the mechanisms behind the complex differences in acidity among varieties that are caused by high altitude are not clear. In this study, we used the ‘Golden Delicious’ apple and its superior variant in the Western Sichuan Plateau of China to analyze organic acid composition, content, and the expression levels of related regulated genes during fruit development. We found that the organic acid content in the variant was significantly lower than that in the ‘Golden Delicious’ apple. In both apples, quinic and malic acids were the predominant organic acids, while citric and tartaric acids were present in lower amounts. In this multidimensional regulatory study, we used transcriptome sequencing, cluster analysis, and weighted gene co-expression network analysis (WGCNA) to reveal that differentially expressed genes are enriched in multiple pathways affecting fruit acidity during apple development; malate dehydrogenase (MDH) affects the malic acid content of fruits of different varieties; and H⁺-ATPase (VHA) mainly regulates the content of vacuolar organic acids, which affects fruit acidity. Additionally, we performed qRT-PCR experiments to validate our results. This study provides molecular insights into the mechanisms by which low-acidity traits form in apples and offers a theoretical basis for regulating the flavor of fleshy fruits. Full article

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

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10 pages, 6258 KiB

Open AccessArticle

Rho-Associated Kinase Inhibitor Fasudil Protects from Sepsis-Induced Acute Kidney Injury in Rat via Suppressing STAT-3 and NLRP-3 Pathway

by Neslihan Şahin, Ejder Saylav Bora, Osman Sezer Çınaroğlu and Oytun Erbaş

Curr. Issues Mol. Biol. 2025, 47(5), 340; https://doi.org/10.3390/cimb47050340 - 8 May 2025

Viewed by 144

Abstract

Sepsis-associated acute kidney injury (S-AKI) is a severe complication in critically ill patients, marked by inflammation, oxidative stress, and renal dysfunction. This study aimed to evaluate the renoprotective effects of Fasudil (Fas), a Rho-associated kinase inhibitor, in a rat model of S-AKI induced [...] Read more.

Sepsis-associated acute kidney injury (S-AKI) is a severe complication in critically ill patients, marked by inflammation, oxidative stress, and renal dysfunction. This study aimed to evaluate the renoprotective effects of Fasudil (Fas), a Rho-associated kinase inhibitor, in a rat model of S-AKI induced by cecal ligation and puncture (CLP). Thirty-six Wistar albino rats were divided into control, CLP with saline, and Fas (100 mg/kg/day intraperitoneally) groups. Biochemical, histopathological, and molecular analyses were conducted to assess kidney function, oxidative stress, and inflammation. Fas treatment significantly decreased plasma malondialdehyde and TNF-α levels, reducing oxidative stress and systemic inflammation. Kidney function markers, including BUN and creatinine, showed marked improvement. Furthermore, Fas suppressed the expression of STAT-3 and NLRP-3 in renal tissues, highlighting its role in modulating key inflammatory pathways. Histological evaluation revealed alleviated renal damage, with less tubular necrosis and interstitial inflammation in the Fas-treated group. In conclusion, Fas demonstrates significant anti-inflammatory, antioxidant, and nephroprotective effects in S-AKI, primarily by inhibiting STAT-3 and NLRP-3 signaling. These results support its potential as a therapeutic agent in sepsis-induced kidney injury and suggest the need for further clinical evaluation. Full article

(This article belongs to the Special Issue New Immunological Therapeutic Strategies in Kidney Disease)

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28 pages, 5671 KiB

Open AccessArticle

Computational Modelling of Tunicamycin C Interaction with Potential Protein Targets: Perspectives from Inverse Docking with Molecular Dynamic Simulation

by Vivash Naidoo, Ikechukwu Achilonu, Sheefa Mirza, Rodney Hull, Jeyalakshmi Kandhavelu, Marushka Soobben and Clement Penny

Curr. Issues Mol. Biol. 2025, 47(5), 339; https://doi.org/10.3390/cimb47050339 - 8 May 2025

Viewed by 163

Abstract

Protein glycosylation plays a crucial role in cancer biology, influencing essential cellular processes such as cell signalling, immune recognition, and tumour metastasis. Therefore, this study highlights the therapeutic potential of targeting glycosylation in cancer treatment, as modulating these modifications could disrupt the fundamental [...] Read more.

Protein glycosylation plays a crucial role in cancer biology, influencing essential cellular processes such as cell signalling, immune recognition, and tumour metastasis. Therefore, this study highlights the therapeutic potential of targeting glycosylation in cancer treatment, as modulating these modifications could disrupt the fundamental mechanisms driving cancer progression and improve therapeutic outcomes. Recently, Tunicamycin C, a well-known glycosylation inhibitor, has shown promise in breast cancer treatment but remains unexplored in colorectal cancer (CRC). Thus, in this study, we aimed to understand the potential action of Tunicamycin C in CRC using in silico studies to identify possible drug targets for Tunicamycin C. First, we identified two target proteins using the HTDocking algorithm followed by GO and KEGG pathway searches: thymidine kinase 1 (TK1) and cAMP-dependent protein kinase catalytic subunit alpha (PKAc). Following this, molecular dynamics modelling revealed that Tunicamycin C binding induced a conformational perturbation in the 3D structures of TK1 and PKAc, inhibiting their activities. This interaction led to a stable design, promoting optimal binding of Tunicamycin C in the hydrophobic pockets of TK1 and PKAc. Serial validation studies highlighted the role of active site residues in binding stabilisation. Tunicamycin C exhibited high binding affinity with TK1 and PKAc. This study provides a way to explore and repurpose novel inhibitors of TK1 and PKAc and identify new therapeutic targets, which may block glycosylation in cancer treatment. Full article

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

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14 pages, 10417 KiB

Open AccessArticle

Mechanistic Insights into the Anti-Hepatocellular Carcinoma Effects of ACY-1215: p53 Acetylation and Ubiquitination Regulation

by Yi Yin, Yutong Du, Yiting Xu, Zhuan Zhu, Yu Hu, Lingling Xu, Kunming Yang, Tian Chen, Yuyang Shi, Chengcheng Wang and Yali Zhang

Curr. Issues Mol. Biol. 2025, 47(5), 338; https://doi.org/10.3390/cimb47050338 - 8 May 2025

Viewed by 183

Abstract

As a major global health challenge, hepatocellular carcinoma (HCC) still faces substantial limitations in its treatment options. This study investigates the anti-HCC potential of ACY-1215, a selective Histone deacetylase 6 (HDAC6) inhibitor, and its mechanism targeting p53 regulation. In vitro studies conducted with [...] Read more.

As a major global health challenge, hepatocellular carcinoma (HCC) still faces substantial limitations in its treatment options. This study investigates the anti-HCC potential of ACY-1215, a selective Histone deacetylase 6 (HDAC6) inhibitor, and its mechanism targeting p53 regulation. In vitro studies conducted with HepG2 and SMMC-7721 cells revealed that ACY-1215 markedly inhibited HCC cell proliferation, migratory capacity, and invasive potential, as evidenced by CCK-8, colony formation, and Transwell assays. Furthermore, ACY-1215 induced caspase-dependent apoptosis. Mechanistically, ACY-1215 enhanced p53 acetylation by disrupting HDAC6-p53 interaction, thereby stabilizing p53 protein levels. Concurrently, it inhibited Murine Double Minute 2 (MDM2)-mediated ubiquitination, blocking proteasomal degradation and prolonging p53 half-life. This dual modulation restored p53 transcriptional activity, leading to the upregulation of downstream effector molecules associated with cell cycle regulation and apoptosis. Collectively, our findings reveal that ACY-1215 exerts potent anti-HCC effects through coordinated regulation of p53 acetylation and ubiquitination, offering a novel dual-targeting strategy for HCC therapy. Full article

(This article belongs to the Section Molecular Medicine)

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6 pages, 187 KiB

Open AccessEditorial

Editorial for Special Issue “Molecular Studies of Female Pregnancy Disorders”

by Alicia Rodríguez Barbero

Curr. Issues Mol. Biol. 2025, 47(5), 337; https://doi.org/10.3390/cimb47050337 - 8 May 2025

Viewed by 119

Abstract

Pregnancy is a complex biological process that requires precise molecular regulation to ensure maternal and fetal health [...] Full article

(This article belongs to the Special Issue Molecular Studies of Female Pregnancy Disorders)

20 pages, 11881 KiB

Open AccessArticle

The 50-nm Free Vesicles Visible in Saccharomyces cerevisiae Are Not COPII-Dependent

by Alexander A. Mironov, Aurora Fusella and Galina V. Beznoussenko

Curr. Issues Mol. Biol. 2025, 47(5), 336; https://doi.org/10.3390/cimb47050336 - 7 May 2025

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Abstract

According to the current dogma, ER–Golgi transport is mediated by COPII-coated vesicles. However, numerous contradictions have emerged in this field. In this study, we demonstrate that Saccharomyces cerevisiae contains three distinct types of membrane spheres, with diameters of approximately 35–45 nm, 47–52 nm, [...] Read more.

According to the current dogma, ER–Golgi transport is mediated by COPII-coated vesicles. However, numerous contradictions have emerged in this field. In this study, we demonstrate that Saccharomyces cerevisiae contains three distinct types of membrane spheres, with diameters of approximately 35–45 nm, 47–52 nm, and over 65 nm, respectively. The first type is Sso1-positive and primary associated with clathrin-positive endocytosis invaginations, which may function as exit sites for secretory soluble cargos. The second population is GOS1-positive and COPI-dependent. The third population represents secretory granules. Furthermore, we propose that several cornerstone studies supporting the COPII-vesicle model can have alternative interpretations. Our findings suggest that the predominant model of intracellular transport in Saccharomyces cerevisiae is the “kiss-and-run” mechanism. Full article

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

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17 pages, 8616 KiB

Open AccessArticle

Biological Characteristics and Genomic Analysis of Acinetobacter nosocomialis Lytic Phage XC1

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

Curr. Issues Mol. Biol. 2025, 47(5), 335; https://doi.org/10.3390/cimb47050335 - 7 May 2025

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Abstract

This study aims to isolate and characterize the lytic phage XC1 targeting Acinetobacter nosocomialis and systematically analyze its biological properties and genomic structure, providing theoretical support for developing novel treatments against antibiotic-resistant infections. Phage XC1 was isolated and purified from lake water. Its [...] Read more.

This study aims to isolate and characterize the lytic phage XC1 targeting Acinetobacter nosocomialis and systematically analyze its biological properties and genomic structure, providing theoretical support for developing novel treatments against antibiotic-resistant infections. Phage XC1 was isolated and purified from lake water. Its morphology, optimal multiplicity of infection (MOI), thermal stability, and pH tolerance were analyzed. Genomic sequencing and functional annotation were performed to identify its lysis-associated genes. Phage XC1 demonstrated a short latent period (20 min) and high burst size (310 plaque-forming units per cell, PFU/cell). It remained stable under temperatures of 50–60 °C and at pH 7, indicating good environmental stability. Genomic analysis revealed a 45,324 bp genome with a GC content of 38.21%, including 84 open reading frames (ORFs), without any lysogenic, virulence, or antibiotic-resistance genes, confirming its safety. Average Nucleotide Identity (ANI) analysis shows that the ANI values between phage XC1 and other phages range from 80% to 95%. As the ANI value between strains of the same species is typically ≥95%, this suggests that phage XC1 may be a previously undiscovered new phage. Classified within the genus Obolenskvirus (class Caudoviricetes), phage XC1 is a virulent bacteriophage with rapid lytic activity and extreme environmental tolerance. Its therapeutic potential against multidrug-resistant infections, either as a monotherapy or in synergy with antibiotics, warrants further investigation. Full article

(This article belongs to the Section Molecular Microbiology)

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10 pages, 1354 KiB

Open AccessCase Report

A Clinical Case of Multisystem Inflammatory Syndrome After SARS-CoV-2 Infection Associated with Group A β-Hemolytic Streptococcus Coinfection and Venous Thrombosis in a Child with Congenital Thrombophilia

by Zdravka Stoyanova, Katya Temelkova, Margarita Ganeva, Teodor Vasilev, Anna Dasheva-Dimitrova, Desislava Kibarova-Hristova and Stefan Stefanov

Curr. Issues Mol. Biol. 2025, 47(5), 334; https://doi.org/10.3390/cimb47050334 - 7 May 2025

Viewed by 91

Abstract

Multisystem inflammatory syndrome in children (MIS-C) is a rare, delayed hyperinflammatory response, which occurs 2–6 weeks after SARS-CoV-2 infection. Main symptoms include fever, involvement of at least two organ systems, elevated inflammatory markers and evidence of infection with or exposure to SARS-CoV-2. While [...] Read more.

Multisystem inflammatory syndrome in children (MIS-C) is a rare, delayed hyperinflammatory response, which occurs 2–6 weeks after SARS-CoV-2 infection. Main symptoms include fever, involvement of at least two organ systems, elevated inflammatory markers and evidence of infection with or exposure to SARS-CoV-2. While the prognosis is generally favorable, complications—such as myocardial dysfunction, coronary aneurysms, and coagulation disorders—can lead to severe outcomes, including death. Immunomodulatory and antithrombotic therapies are key components of treatment. We report a clinical case of a 3-year-old boy who developed MIS-C, initially presenting with fever, multiorgan involvement, and confirmed SARS-CoV-2 infection, along with a coinfection caused by group A β-hemolytic Streptococcus (GAS) isolated from throat culture. On the ninth day of illness, thrombosis of the right subclavian vein was detected. Subsequent genetic testing for thrombophilia revealed that the patient was a heterozygous carrier of Factor V Leiden, Factor V HR2, and PAI-1 4G/5G polymorphisms. Thromboembolic events (TEs) are serious and potentially life-threatening complications of MIS-C. This case highlights the occurrence of TE in a 3-year-old boy, an age group younger than typically observed, emphasizing the need for heightened awareness, early detection, and prompt intervention. Additionally, it underscores the importance of careful monitoring of thrombotic risks in MIS-C patients, particularly those with underlying prothrombotic conditions, to prevent severe outcomes. 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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22 pages, 6932 KiB

Open AccessArticle

Antiviral Activity of Rhamnolipids Nano-Micelles Against Rhinoviruses—In Silico Docking, Molecular Dynamic Analysis and In-Vitro Studies

by Lila Touabi, Nasser S. M. Ismail, Marwa R. Bakkar, Gary R. McLean and Yasmin Abo-zeid

Curr. Issues Mol. Biol. 2025, 47(5), 333; https://doi.org/10.3390/cimb47050333 - 6 May 2025

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Abstract

Hospital-acquired infections (HAIs) previously focused mainly on multidrug-resistant (MDR) bacteria, with less attention on viruses. The COVID-19 pandemic highlighted the importance of controlling viral infections. Human rhinoviruses (HRVs) are among the viruses responsible for HAIs. HRVs are non-enveloped viruses that infect the upper [...] Read more.

Hospital-acquired infections (HAIs) previously focused mainly on multidrug-resistant (MDR) bacteria, with less attention on viruses. The COVID-19 pandemic highlighted the importance of controlling viral infections. Human rhinoviruses (HRVs) are among the viruses responsible for HAIs. HRVs are non-enveloped viruses that infect the upper airways after airborne or direct transmission. Due to their lack of a membrane envelope, HRVs exhibit moderate resistance to commonly applied alcoholic disinfectants. Therefore, there is a significant need to develop alternative disinfection and hand sanitation strategies to control HRV infections in healthcare settings without posing a risk to human health. The antimicrobial activity and safety of rhamnolipids and rhamnolipids nano-micelles (RMN) against MDR-bacteria and several viruses, including SARS-CoV-2, were confirmed recently. Also, we previously demonstrated the superior antimicrobial activity of RMN over rhamnolipids. In the current study, molecular docking demonstrated the weak interactions of rhamnolipids with HRV-1A (minor group) compared to HRV-14 (major group), suggesting a superior antiviral activity of rhamnolipids towards major group rhinoviruses. To biologically validate these data, RMN was prepared and characterized, and then antiviral activity against HRV-16 (major group) and HRV-1B (minor group) infection of HeLa cells was assessed. RMN showed a complete inhibition of HRV-16 infection with recovery of 100% of HeLa cell viability. In contrast, only partial inhibition of HRV-1B infection with approximately 50% protection against infection was observed. Therefore, RMN might be recommended as a disinfectant and/or a hand sanitizer component to control the spread of RVs in hospital care settings or elsewhere to reduce the incidence of respiratory infections. Full article

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

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37 pages, 2032 KiB

Open AccessReview

Galectin-3 in Cardiovascular Health: A Narrative Review Based on Life’s Essential 8 and Life’s Simple 7 Frameworks

by Adrian Martuszewski, Patrycja Paluszkiewicz, Rafał Poręba and Paweł Gać

Curr. Issues Mol. Biol. 2025, 47(5), 332; https://doi.org/10.3390/cimb47050332 - 6 May 2025

Viewed by 173

Abstract

Gal-3, also known as galectin-3, a lectin that binds β-galactosides, has gained attention as a novel biomarker and pathophysiological mediator in cardiovascular disease, where it contributes to inflammation, fibrosis, metabolic dysregulation and cardiac remodeling. This narrative review, developed following SANRA (Scale for the [...] Read more.

Gal-3, also known as galectin-3, a lectin that binds β-galactosides, has gained attention as a novel biomarker and pathophysiological mediator in cardiovascular disease, where it contributes to inflammation, fibrosis, metabolic dysregulation and cardiac remodeling. This narrative review, developed following SANRA (Scale for the Assessment of Narrative Review Articles) guidelines, aims to integrate current clinical and experimental findings on gal-3 into the American Heart Association Life’s Simple 7 (LS7) and Life’s Essential 8 (LE8). By thematically organizing our review across modifiable domains of cardiovascular health, including glucose regulation, lipid metabolism, physical activity, blood pressure, diet, sleep, tobacco use, and body weight (BMI, body mass index), we highlight the role of gal-3 in linking environmental, behavioral and molecular risk factors to cardiometabolic outcomes. Particular attention is given to the oxidative stress, inflammatory–fibrotic axis, and immune activation as mechanistic pathways underlying gal-3-associated cardiovascular damage. We also discuss its relevance to public health and prevention, considering gal-3’s potential for early risk stratification, monitoring lifestyle interventions and personalized prevention strategies. This review bridges molecular mechanisms with clinical and public health relevance, particularly in the context of environmental and lifestyle-related cardiovascular risk. Full article

(This article belongs to the Special Issue Effects of Environmental Factors on Cardiovascular Disease: From Molecular Effects to Possible Future Clinic Application)

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15 pages, 8169 KiB

Open AccessArticle

The TRHDE and TSHR Genes Regulate Laying Traits in Domesticated Zi Geese

by Xiuhua Zhao, Shan Yue, Yuanliang Zhang, Jinyan Sun, Fugang Peng and Zhenhua Guo

Curr. Issues Mol. Biol. 2025, 47(5), 331; https://doi.org/10.3390/cimb47050331 - 4 May 2025

Viewed by 187

Abstract

Domestic geese are typically seasonal breeders, and the timing and number of eggs they lay vary depending on the region and breed. Previous studies evaluated the Zi goose, which is currently the domestic goose breed with the highest egg production. This research divided [...] Read more.

Domestic geese are typically seasonal breeders, and the timing and number of eggs they lay vary depending on the region and breed. Previous studies evaluated the Zi goose, which is currently the domestic goose breed with the highest egg production. This research divided the reproductive cycle into four periods and compared the ovarian RNA-seq and DNA methylation data of Zi geese across these time points to identify the key genes that increase egg production. By integrating differentially expressed genes and differentially methylated genes, we identified 525 candidate genes that presented upregulated expression and hypomethylated regions (the hypo-up group). Ultimately, we found that the thyrotropin-releasing hormone degrading enzyme (TRHDE) and thyroid-stimulating hormone receptor (TSHR) genes play a crucial role in regulating the reproductive cycle of Zi geese. We also generated a proposed model of the relationship between the TRHDE and TSHR genes in Zi geese. This study provides theoretical references for the development of egg-laying goose breeds and raises additional scientific questions for further discussion among researchers. Full article

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

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19 pages, 1261 KiB

Open AccessReview

CRISPR-Cas9 in the Tailoring of Genetically Engineered Animals

by Wiktoria Urban, Marta Kropacz, Maksymilian Łach and Anna Jankowska

Curr. Issues Mol. Biol. 2025, 47(5), 330; https://doi.org/10.3390/cimb47050330 - 4 May 2025

Viewed by 666

Abstract

CRISPR-Cas9 enables targeted genome editing and has become a pivotal tool in biomedical research and animal genome engineering. This review highlights its application in generating genetically modified animals used as preclinical disease models, bioreactors for recombinant protein production, and potential sources of xenotransplantation [...] Read more.

CRISPR-Cas9 enables targeted genome editing and has become a pivotal tool in biomedical research and animal genome engineering. This review highlights its application in generating genetically modified animals used as preclinical disease models, bioreactors for recombinant protein production, and potential sources of xenotransplantation organs. We also discuss its role in improving livestock traits, welfare, and breeding efficiency. The benefits and limitations of CRISPR-Cas9 are examined, emphasizing its transformative potential in research and agricultural biotechnology. Full article

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

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16 pages, 5080 KiB

Open AccessArticle

Exploring the Therapeutic Potential of Rehmannia glutinosa: A Network Pharmacology and Molecular Docking Analysis Across Multiple Diseases

by Jinyoung Park, Muhammad Yasir, Eun-Taek Han, Jin-Hee Han, Won Sun Park, Jongseon Choe and Wanjoo Chun

Curr. Issues Mol. Biol. 2025, 47(5), 329; https://doi.org/10.3390/cimb47050329 - 3 May 2025

Viewed by 171

Abstract

Rehmannia glutinosa (RG), a fundamental herb in traditional Chinese medicine belonging to the Orobanchaceae family, has been widely used for centuries due to its diverse therapeutic properties, including promoting blood circulation, enhancing immunity, managing diabetes, reducing inflammation, and supporting kidney function. Despite its [...] Read more.

Rehmannia glutinosa (RG), a fundamental herb in traditional Chinese medicine belonging to the Orobanchaceae family, has been widely used for centuries due to its diverse therapeutic properties, including promoting blood circulation, enhancing immunity, managing diabetes, reducing inflammation, and supporting kidney function. Despite its traditional significance, scientific studies on RG’s therapeutic mechanisms remain limited, and its underlying pharmacological pathways are not extensively elucidated. This study employed network pharmacology and molecular docking to identify RG’s active compounds and investigate their therapeutic potential in allergy, anemia, diabetes, and menopause. From an initial pool of 122 compounds, 50 bioactive compounds were screened based on bioavailability and drug-likeness, resulting in 40 active compounds and 11 target proteins closely associated with these conditions. Key active compounds identified included iridoid glycosides (rehmaglutin A, B, C, D, jioglutin A, B, C, jioglutolide) and other bioactive molecules such as caffeic acid, geraniol, 5-hydroxytryptamine, melatonin, and rhodioloside. Molecular docking technology was employed to verify the stable binding of target proteins with active compounds. Protein–protein interaction (PPI) analysis revealed that RG’s core target proteins are central to pathways regulating inflammation, cell survival, apoptosis, and immune response. Enrichment analyses demonstrated that RG’s target proteins intersect significantly with pathways including the AGE-RAGE signaling pathway in diabetic complications, IL-17, HIF-1 signaling, and neuroactive ligand-receptor interactions, all of which are essential in managing diabetes and menopause symptoms. These findings underscore RG’s multi-target therapeutic potential, particularly in modulating immunity, metabolism, and inflammation. This study highlights RG’s potential as a therapeutic agent and provides a framework for future research to further elucidate its mechanisms and support the development of targeted drugs based on RG’s active compounds. Full article

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

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18 pages, 11294 KiB

Open AccessArticle

Investigating the Therapeutic Potential of Crude Leech Saliva Based on Its Anticancer, Antioxidant, and Anti-Inflammatory Effects

by Alican Bilden, İlhan Sabancılar, Serap Yalçın Azarkan, Kenan Karadağlı, Seçkin Kaya, Merve Kahraman and Muttalip Çiçek

Curr. Issues Mol. Biol. 2025, 47(5), 328; https://doi.org/10.3390/cimb47050328 - 3 May 2025

Viewed by 198

Abstract

Leech therapy is a biotherapeutic approach that has been traditionally used for centuries and is currently being re-evaluated in modern medicine. The efficacy of this treatment is attributed to various bioactive compounds found in leech saliva, which exhibit anticoagulant, anti-inflammatory, antioxidant, and anticancer [...] Read more.

Leech therapy is a biotherapeutic approach that has been traditionally used for centuries and is currently being re-evaluated in modern medicine. The efficacy of this treatment is attributed to various bioactive compounds found in leech saliva, which exhibit anticoagulant, anti-inflammatory, antioxidant, and anticancer properties. It has been demonstrated that leech saliva possesses the potential to modulate inflammatory processes and apoptotic mechanisms. In this study, the therapeutic potential of the saliva of Hirudo verbana was evaluated, and its biological and pharmacological effects were comprehensively investigated. The anticancer effects, antioxidant capacity, and anti-inflammatory activity of the crude leech saliva were assessed using human umbilical vein endothelial cells and epithelial ovarian cancer cells. The chemical composition of the saliva was analyzed using gas chromatography–mass spectrometry, while the protein content was determined by the Bradford assay. Antioxidant activity was measured using the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay, inflammatory effects were evaluated by Enzyme-Linked ImmunoSorbent Assay, and cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The findings revealed that crude leech saliva had a minimal effect on healthy cells but showed a selective effect on the viability of ovarian cancer cells. At low concentrations (3.13%), 99.16% of healthy cells remained viable, whereas this rate decreased to 89.25% in cancer cells; at high concentrations (50%), cell viability in cancer cells declined to 63.02%. Gas chromatography–mass spectrometry analysis identified compounds such as gibberellic acid and 6-[(4-methoxyphenyl)methoxy]-4,4,5,7,8-pentamethyl-3H-chromen-2-one, which demonstrated high affinity for the antiapoptotic proteins Bcl-2 and Survivin in molecular docking analyses. In conclusion, the crude leech saliva was confirmed to possess anti-inflammatory, antioxidant, and anticancer properties. However, further biochemical and clinical research is needed to elucidate the underlying mechanisms of these biological effects in greater detail. Full article

(This article belongs to the Section Bioorganic Chemistry and Medicinal Chemistry)

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17 pages, 2074 KiB

Open AccessArticle

Mesalazine and Lactoferrin as Potential Adjuvant Therapy in Colorectal Cancer: Effects on Cell Viability and Wnt/β-Catenin Pathway

by Joanna Słoka, Marcel Madej, Ilona Nowak and Barbara Strzałka-Mrozik

Curr. Issues Mol. Biol. 2025, 47(5), 327; https://doi.org/10.3390/cimb47050327 - 2 May 2025

Viewed by 193

Abstract

Colorectal cancer (CRC) remains one of the leading causes of cancer-related deaths, meaning it is essential to explore all possible strategies for its prevention and treatment. Unfortunately, risk factors such as an unhealthy lifestyle, lack of exercise, and obesity—which are increasingly prevalent in [...] Read more.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related deaths, meaning it is essential to explore all possible strategies for its prevention and treatment. Unfortunately, risk factors such as an unhealthy lifestyle, lack of exercise, and obesity—which are increasingly prevalent in developed countries—contribute to CRC development. The aim of this study was to evaluate the effect of a mesalazine (MES) and lactoferrin (LACT) combination on the viability of CRC cells and healthy intestinal epithelial cells, as well as to assess the expression profile of target genes within the Wnt/β-catenin pathway. Additionally, this study aimed to preliminarily analyze the mechanism of action underlying the combined effects of these compounds. In this study, we used three CRC cell lines (HCT-116, DLD-1, and HT-29) along with the healthy intestinal epithelial cell line CCD 841 CoN. These cells were treated with MES and LACT separately, as well as in combination. We demonstrated that the combination of MES and LACT reduced the viability of CRC cells more effectively than either compound alone, while slightly increasing the viability of normal intestinal epithelial cells. The synergistic effect of MES and LACT may serve as a foundation for developing new treatment strategies for CRC, utilizing compounds with a high safety profile. Full article

(This article belongs to the Section Molecular Medicine)

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18 pages, 2588 KiB

Open AccessArticle

Glutathione Peroxidase 4 in Blunt Snout Bream (Megalobrama amblycephala) Regulates Ferroptosis and Inflammation in Response to Aeromonas hydrophila Infection

by Miao He, Huanling Wang and Hong Liu

Curr. Issues Mol. Biol. 2025, 47(5), 326; https://doi.org/10.3390/cimb47050326 - 2 May 2025

Viewed by 149

Abstract

Glutathione peroxidase 4 (GPX4) plays a crucial role in regulating lipid peroxidation and is associated with infection and inflammation, particularly in terms of its effects on inflammatory cytokines and ferroptosis. This study aimed to investigate the regulatory effects of Gpx4 on the inflammatory [...] Read more.

Glutathione peroxidase 4 (GPX4) plays a crucial role in regulating lipid peroxidation and is associated with infection and inflammation, particularly in terms of its effects on inflammatory cytokines and ferroptosis. This study aimed to investigate the regulatory effects of Gpx4 on the inflammatory response and ferroptosis in blunt snout bream (Megalobrama amblycephala), a significant freshwater fish species in China, after Aeromonas hydrophila infection. Using a bioinformatics analysis, we discovered that Gpx4 has a conserved protein structure and high amino acid identity in various carp species, indicating functional conservation across species and through involution. RT-qPCR analysis revealed that gpx4 mRNA increased after the neuroembryonic stage during early development and was particularly highly expressed in the liver of healthy adult fish. Upon A. hydrophila infection, gpx4 expression decreased significantly and rapidly in the liver. In L8824 cells, overexpression of gpx4 suppressed inflammatory cytokines and inhibited ferroptosis in response to both A. hydrophila infection and induction of ferroptosis-inducer RSL3. These findings highlight the regulatory role of Gpx4 in cellular ferroptosis and inflammation, providing insights into the complex mechanisms of disease resistance and potentially aiding in the development of strategies for disease control in fish. Full article

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

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21 pages, 3108 KiB

Open AccessArticle

Caprylic Acid Restores Branched-Chain Amino Acid Metabolism in a Mouse Cachexia Model

by Isao Kawahara, Rina Fujiwara-Tani, Takuya Mori, Shota Nukaga, Ryoichi Nishida, Yoshihiro Miyagawa, Kei Goto, Hitoshi Ohmori, Kiyomu Fujii, Yi Luo, Takamitsu Sasaki, Chie Nakashima, Ruiko Ogata and Hiroki Kuniyasu

Curr. Issues Mol. Biol. 2025, 47(5), 325; https://doi.org/10.3390/cimb47050325 - 1 May 2025

Viewed by 224

Abstract

Cancer-associated sarcopenia is closely linked to the prognosis of cancer patients, making its management a critical aspect of cancer treatment. Branched-chain amino acids (BCAAs) are known to promote skeletal muscle growth in healthy individuals; however, their efficacy in cancer patients remains controversial. In [...] Read more.

Cancer-associated sarcopenia is closely linked to the prognosis of cancer patients, making its management a critical aspect of cancer treatment. Branched-chain amino acids (BCAAs) are known to promote skeletal muscle growth in healthy individuals; however, their efficacy in cancer patients remains controversial. In this study, we investigated the effects of BCAAs on cancer-associated sarcopenia to identify the underlying mechanisms that may suppress their effectiveness. In both a mouse cachexia model and an in vitro cachexia model, BCAAs did not significantly reduce oxidative stress, improve oxidative phosphorylation, suppress cytokine production, or enhance muscle mass and maturation, as observed in non-cancer-bearing models. Furthermore, treatment with 5-fluorouracil exacerbated sarcopenia in the mouse cachexia model, independent of tumor weight reduction, and this deterioration was not ameliorated by a BCAA-supplemented diet. The ineffectiveness of BCAAs was attributed to impaired BCAA catabolism, characterized by the decreased expression of branched-chain α-ketoacid dehydrogenase (BCKD) and increased levels of its inactive phosphorylated form, which were driven by elevated expression of BCKD kinase. These metabolic alterations were induced by high-mobility group box-1 (HMGB1). Notably, caprylic acid reversed these impairments in BCAA metabolism, thereby restoring BCAA efficacy. Our findings suggest that enhancing BCAA metabolism may improve their therapeutic potential in the treatment of cancer-associated sarcopenia. Full article

(This article belongs to the Special Issue Tumor Microenvironment: Crosstalk Between Epigenetics, Metabolism and Immunity)

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19 pages, 4449 KiB

Open AccessArticle

Ultra-High-Performance Liquid Chromatography–Tandem Mass Spectrometry and Network Pharmacology Reveal the Mechanisms of Rhodiola crenulata in Improving Non-Alcoholic Fatty Liver Disease

by Xin Zeng, Jianwei Wang, Qinyi Xu, Chengdan Deng, Xi Yi, Shang Wang, Ling Yao and Wei Xiang

Curr. Issues Mol. Biol. 2025, 47(5), 324; https://doi.org/10.3390/cimb47050324 - 1 May 2025

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Abstract

Rhodiola crenulata (RC) is a traditional herb and functional food that has demonstrated beneficial effects in improving physical function, enhancing work capacity, alleviating fatigue, and preventing altitude sickness. Additionally, RC has shown promising effects in the treatment of non-alcoholic fatty liver disease (NAFLD), [...] Read more.

Rhodiola crenulata (RC) is a traditional herb and functional food that has demonstrated beneficial effects in improving physical function, enhancing work capacity, alleviating fatigue, and preventing altitude sickness. Additionally, RC has shown promising effects in the treatment of non-alcoholic fatty liver disease (NAFLD), although its specific bioactive components and underlying mechanisms remain unclear. In this study, ultra-high-performance liquid chromatography–mass spectrometry (UHPLC-MS) combined with network pharmacology was employed to identify six potential bioactive compounds from the serum of rats treated with RC—Salidroside, Tyrosol, Crenulatin, Catechin gallate, Eriodictyol, and Rhodiooctanoside—that may contribute to its therapeutic effects on NAFLD. The efficacy of these compounds in improving NAFLD was assessed in vitro using HepG2 cells exposed to Palmitic acid (PA), and it was found that Catechin gallate exhibited a significant effect in reducing lipid accumulation in HepG2 cells. Furthermore, based on network pharmacology predictions, molecular docking studies suggested that the primary targets of Catechin gallate in alleviating fatty liver might include ABCB1, DYRK1A, PGD, and FUT4. Molecular dynamics simulations revealed stable binding interactions between Catechin gallate and these four target proteins. This study clarifies the material basis of RC in the treatment of NAFLD and provides a theoretical foundation for the application of RC and Catechin gallate as functional additives for the management of NAFLD. Full article

(This article belongs to the Special Issue Molecular Mechanisms Underlying Fatty Liver Disease: From Pathogenesis to Treatment, 2nd Edition)

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Curr. Issues Mol. Biol., Volume 47, Issue 5 (May 2025) – 59 articles

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