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Curr. Issues Mol. Biol., Volume 47, Issue 5 (May 2025) – 69 articles

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2 pages, 148 KiB  
Editorial
Editorial for Special Issue “Current Advances in Oxytocin Research”
by Claudia Camerino
Curr. Issues Mol. Biol. 2025, 47(5), 363; https://doi.org/10.3390/cimb47050363 (registering DOI) - 15 May 2025
Abstract
Very few hormones and neurotransmitters are as fascinating as oxytocin [...] Full article
(This article belongs to the Special Issue Current Advances in Oxytocin Research)
18 pages, 804 KiB  
Review
Herbal Medicine in Breast Cancer Therapy: Mechanisms, Evidence, and Future Perspectives
by Hsien-Chang Wu, Chung-Che Tsai, Po-Chih Hsu and Chan-Yen Kuo
Curr. Issues Mol. Biol. 2025, 47(5), 362; https://doi.org/10.3390/cimb47050362 - 15 May 2025
Abstract
Breast cancer remains a leading global cause of cancer-related mortality among women, requiring the development of safer and more effective therapeutic strategies. Herbal medicines have gained increasing attention as complementary approaches due to their multi-targeted actions, more limited toxicities, and the potential ability [...] Read more.
Breast cancer remains a leading global cause of cancer-related mortality among women, requiring the development of safer and more effective therapeutic strategies. Herbal medicines have gained increasing attention as complementary approaches due to their multi-targeted actions, more limited toxicities, and the potential ability to overcome resistance associated with conventional treatments. This review highlights the antitumor properties and underlying mechanisms of several well-studied herbal compounds, including curcumin, resveratrol, epigallocatechin gallate, withaferin A, thymoquinone, baicalin, berberine, Oldenlandia diffusa, and Salvia miltiorrhiza. These phytochemicals exert antitumor effects by inducing apoptosis, inhibiting cell proliferation and metastasis, modulating immune responses, and sensitizing tumor cells to chemotherapy and radiotherapy. Furthermore, many of these agents regulate key signaling pathways, such as nuclear factor kappa-light-chain-enhancer of activated B cells, phosphatidylinositol 3-kinase/AKT, p53, signal transducer and activator of transcription 3, and extracellular signal-regulated kinases 1/2, and the tumor microenvironment. Despite promising preclinical and early clinical evidence, challenges remain regarding the bioavailability, standardization, and large-scale clinical validation of these phytochemicals. This review underscores the therapeutic potential of herbal medicines in breast cancer treatment and advocates for further research to facilitate their integration into evidence-based oncology practice. Full article
(This article belongs to the Special Issue Natural Compounds: An Adjuvant Strategy in Cancer Management)
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21 pages, 10277 KiB  
Article
Impact of SARS-CoV-2 Variant NSP6 on Pathogenicity: Genetic Analysis and Cell Biology
by Yangye Gao, Peng Ni, Yanqiao Hua, Shuaiyin Chen and Rongguang Zhang
Curr. Issues Mol. Biol. 2025, 47(5), 361; https://doi.org/10.3390/cimb47050361 - 14 May 2025
Abstract
SARS-CoV-2 nonstructural protein (NSP) 6 is one of the factors affecting viral pathogenicity. Mutations in NSP6 continuously emerge during viral transmission and are closely associated with alterations in viral pathogenicity. This study investigated the structural and functional impacts of NSP6 mutations by analyzing [...] Read more.
SARS-CoV-2 nonstructural protein (NSP) 6 is one of the factors affecting viral pathogenicity. Mutations in NSP6 continuously emerge during viral transmission and are closely associated with alterations in viral pathogenicity. This study investigated the structural and functional impacts of NSP6 mutations by analyzing NSP6 proteins from the Wuhan-Hu-1/B (WT) strain and predominant variants Alpha, XBB.1.16, BA.2.86, and JN.1 using bioinformatics, transcriptomics, and cellular experiments. The results demonstrate that the V3593F mutation decreased the β-sheet proportion and modified hydrogen bonding patterns, while the L3829F mutation enhanced structural stability by promoting random coils. The R3821K substitution exposed lysine residues, potentially enhancing molecular interactions. Combined transcriptomic profiling and functional assays revealed that WT-NSP6 significantly inhibited poly (I: C)-induced immune factor transcription and reduced the phosphorylation levels of p-IRF3 and p-STAT1, effects absent in the XBB.1.16 variant. Furthermore, WT-NSP6 markedly activated p-AKT and p-mTOR expression, with JN.1-NSP6 maintaining limited capacity to upregulate p-mTOR. However, p53 inhibitor treatment reversed Alpha-NSP6- and BA.2.86-NSP6-upregulated p-mTOR protein expression in cells. This study demonstrates that a high frequency of NSP6 mutations alters NSP6’s structure, impairing the type I interferon signaling pathway and affecting host antiviral responses through the p53-AKT-mTOR signaling pathway. These findings contribute to the understanding of evolution, immune evasion, and viral pathogenesis mechanisms, with potential implications for the development of antiviral therapies and preventive strategies for this viral infection. Full article
(This article belongs to the Section Molecular Microbiology)
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15 pages, 4213 KiB  
Article
Dose-Dependent Effects of TGF-β Inhibition on Osteoblast Differentiation and Wound Healing
by Nihal Almuraikhi, Latifa Alkhamees, Sumaiya Tareen, Hessah Alshammari and Manikandan Muthurangan
Curr. Issues Mol. Biol. 2025, 47(5), 360; https://doi.org/10.3390/cimb47050360 - 14 May 2025
Abstract
TGF-β is a multifunctional pathway that controls significant cellular and physiological processes and several pathological activities. TGF-β-induced signaling can be triggered upon binding to specific receptors to initiate the transcriptional activation of several genes and cellular processes. However, the detailed role of TGF-β [...] Read more.
TGF-β is a multifunctional pathway that controls significant cellular and physiological processes and several pathological activities. TGF-β-induced signaling can be triggered upon binding to specific receptors to initiate the transcriptional activation of several genes and cellular processes. However, the detailed role of TGF-β signaling in osteoblast differentiation remains to be explicated. SB525334, a selective TGF-βRI inhibitor, was investigated for its effect on the osteoblastic differentiation of human bone marrow MSCs at different concentrations. Alkaline phosphatase (ALP) activity was used to assess osteoblast differentiation marker, while Alizarin red staining was used as a marker for mineralization. Expressions of osteoblast-specific genes were evaluated using real-time PCR. A migration assay was performed to assess the effect of TGF-β on wound healing. Moreover, immunofluorescent staining for SMAD2/3 and SMAD4 was employed to confirm the activation of the TGF-β pathway. The inhibition of TGF-β1 signaling using a high concentration of SB525334 (3 µM) significantly reduced ALP activity and mineralization and downregulated osteoblast-specific genes. However, the opposite effect was reported using a lower concentration (0.03 µM), where osteoblast-associated genes were significantly upregulated, and ALP activity and mineralization were higher. Significant scratch/wound healing was achieved at a lower concentration of SB525334, while a higher concentration of SB525334 resulted in lower healing. Moreover, a low concentration of SB525334 demonstrated nuclear translocation of SMAD 2/3 and 4. Our study confirms that the effect of TGF-β signaling in bone formation and wound healing is dose-dependent, and the use of TGF-β is recommended as a valuable therapeutic approach. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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19 pages, 2190 KiB  
Article
Evaluation of the Expression of IDO and PTEN in Human Kidney Cancer
by Gábor Kónya, Zsuzsanna Szabó, Nikoletta Dobos, József Király, Krisztián Szegedi, Anna Vass, Ákos Steli, Csaba Szász, Balázs Dezső, Barbara Zsebik and Gábor Halmos
Curr. Issues Mol. Biol. 2025, 47(5), 359; https://doi.org/10.3390/cimb47050359 - 13 May 2025
Viewed by 35
Abstract
Immunotherapy has become one of the primary forms of cancer treatment. The inhibition of immune checkpoint molecules, including indoleamine 2,3-dioxygenase (IDO), is a promising approach for immunotherapy. Phosphatase and tensin homolog (PTEN) is well known as a tumor suppressor that antagonizes oncogenic signaling [...] Read more.
Immunotherapy has become one of the primary forms of cancer treatment. The inhibition of immune checkpoint molecules, including indoleamine 2,3-dioxygenase (IDO), is a promising approach for immunotherapy. Phosphatase and tensin homolog (PTEN) is well known as a tumor suppressor that antagonizes oncogenic signaling molecules/pathways and plays a key role in the prognosis and (immuno)therapy of the disease. In this study, twenty healthy and tumorous renal tissue pairs were investigated, and the mRNA (RT-qPCR) and protein (Western blot) expression of IDO and PTEN were analyzed. In two cancer cell lines (CAKI-2; A-498), the protein of IDO and PTEN was measured followed by IDO induction with interferon alpha-2 (IFN-α2). According to our results, a significantly higher mRNA expression of IDO and PTEN was found in tumorous tissues compared to the adjacent healthy kidney specimens. The mRNA expression of IDO and PTEN showed a positive correlation in 80% of the sample pairs. Western blot results confirmed the protein expression of both IDO and PTEN. In the cell lines, immunocytochemistry showed that IDO is inducible with IFN-α2. In summary, our results suggest that IDO expression may play a role in the development of renal cancer, and IDO as well as PTEN might be potential biomarkers for patients with RCC. Full article
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21 pages, 6696 KiB  
Article
Ethanol Extract of Adlay Hulls Suppresses Acute Myeloid Leukemia Cell Proliferation via PI3K/Akt Pathway Inhibition
by Guangjie Li, Wenyuan Yang, Jiahui Xu, Ziqian Liu, Zhijian Li, Xiaoqiu Wu, Tongtong Li, Ruoxian Wang, Yamin Zhu and Ning Liu
Curr. Issues Mol. Biol. 2025, 47(5), 358; https://doi.org/10.3390/cimb47050358 - 13 May 2025
Viewed by 51
Abstract
Acute myeloid leukemia (AML) is a common hematologic malignancy in the elderly with frequent relapse and poor prognosis. Limited treatments highlight the need for novel natural anticancer compounds. Adlay, valued for its medicinal and dietary properties, exhibits anti-inflammatory and anticancer effects. However, research [...] Read more.
Acute myeloid leukemia (AML) is a common hematologic malignancy in the elderly with frequent relapse and poor prognosis. Limited treatments highlight the need for novel natural anticancer compounds. Adlay, valued for its medicinal and dietary properties, exhibits anti-inflammatory and anticancer effects. However, research on adlay hulls, particularly their anti-AML bioactive molecules, remains insufficient. This study evaluated the effects of adlay hull ethanol extract (AHE) on AML cell proliferation and apoptosis. AHE was extracted with ethanol and fractionated using n-hexane, ethyl acetate, and n-butanol, followed by silica gel chromatography. Cytotoxicity was assessed via the CCK-8 assay, and mechanisms were analyzed by flow cytometry and Western blotting. The bioactive components were characterized by UPLC-IMS-QTOF-MS. AHE-EA-C (ethyl acetate fraction C) inhibited AML cell proliferation, induced G0/G1 phase arrest, and promoted apoptosis. It suppressed the PI3K/Akt pathway by reducing PI3K and Akt phosphorylation. Using UPLC-IMS-QTOF-MS analysis, a total of 52 compounds with potential anti-AML activity were identified in AHE-EA-C, among which neohesperidin and cycloartanol have been previously reported to exhibit anti-AML activity and thus hold promise as candidates for further development as AML inhibitors. This study is the first to identify adlay hull bioactive components and their anti-AML mechanisms via PI3K/Akt pathway inhibition, providing a foundation for developing natural anti-AML therapies. Full article
(This article belongs to the Section Bioorganic Chemistry and Medicinal Chemistry)
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15 pages, 542 KiB  
Review
The Mechanisms of Chronic Inflammation in Obesity and Potential Therapeutic Strategies: A Narrative Review
by Elvira Meni Maria Gkrinia and Andrej Belančić
Curr. Issues Mol. Biol. 2025, 47(5), 357; https://doi.org/10.3390/cimb47050357 - 13 May 2025
Viewed by 62
Abstract
Obesity, a global health concern of increasing significance, is characterized by chronic low-grade inflammation (LGCI) that significantly contributes to metabolic dysfunction. This narrative review explores the intricate pathophysiological mechanisms driving LGCI in obesity, emphasizing the role of adipose tissue, immune cell activation, and [...] Read more.
Obesity, a global health concern of increasing significance, is characterized by chronic low-grade inflammation (LGCI) that significantly contributes to metabolic dysfunction. This narrative review explores the intricate pathophysiological mechanisms driving LGCI in obesity, emphasizing the role of adipose tissue, immune cell activation, and inflammatory signaling pathways. Hypertrophic adipocytes and infiltrating immune cells, particularly macrophages, release a cascade of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, creating a self-perpetuating cycle of inflammation. These mediators disrupt insulin signaling through JNK and NF-κB pathway activation, leading to systemic insulin resistance, cardiovascular complications, gut dysbiosis and other metabolic disorders. The review further discusses therapeutic strategies to mitigate obesity-related LGCI, focusing on lifestyle interventions, nutritional approaches, and pharmacological agents. Physical activity, specific nutrients, and dietary patterns can modulate inflammatory responses, while anti-obesogenic medicines and bariatric procedures offer additional avenues for intervention. By understanding and addressing the root causes of inflammation in obesity, healthcare professionals can develop targeted strategies to improve metabolic health and overall well-being of individuals with obesity and, ultimately, prevent and manage the wide-ranging complications associated with this condition. Full article
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13 pages, 3171 KiB  
Article
K-Homology Splicing Regulatory Protein (KSRP) Augments Survival and Proliferation of Human Melanoma Cells
by Harunur Rashid, Mohammad Asif Sherwani, Jung Vin Seo, Azeem Ahmad, Sumaiya Tasnim, Quamarul Hassan and Nabiha Yusuf
Curr. Issues Mol. Biol. 2025, 47(5), 356; https://doi.org/10.3390/cimb47050356 - 13 May 2025
Viewed by 55
Abstract
Melanoma is one of the most aggressive and fatal cancers; however, effective and long-lasting treatment options for melanoma continue to be sought after due to the development of resistance mechanisms to the currently available therapies. Background: The K-homology-type splicing regulatory protein (KSRP) is [...] Read more.
Melanoma is one of the most aggressive and fatal cancers; however, effective and long-lasting treatment options for melanoma continue to be sought after due to the development of resistance mechanisms to the currently available therapies. Background: The K-homology-type splicing regulatory protein (KSRP) is an RNA-binding regulatory protein that binds to the AU-rich elements at the 3′-UTR of target mRNAs. Prior studies have demonstrated that KSRP plays a crucial role in the post-transcriptional regulation of gene expression in human melanoma. Subsequently, in this study, we further examined the role of KSRP in cell migration, colony formation, apoptosis, and tumorigenicity of human melanoma. Methods: KSRP was knocked down in two different human melanoma cell lines: A375 and SK-MEL-28, using lenti-shRNA techniques. By doing so, we studied the effects of KSRP inhibition on cell migration, colony formation, proliferation, apoptosis, and tumorigenicity in these melanoma cell lines. Results: We observed a significant decrease in cell migration, colony formation, proliferation, and tumorigenicity, while also observing a substantial increase in apoptosis in the KSRP knock down melanoma cell lines. Conclusions: Our data establishes that KSRP plays a vital role in cell migration, colony formation, proliferation, apoptosis, and tumorigenicity in both the A375 and SK-MEL-28 human melanoma cell lines. Full article
(This article belongs to the Special Issue Targeting Tumor Microenvironment for Cancer Therapy, 3rd Edition)
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7 pages, 861 KiB  
Communication
Construction and Evaluation of a HCoV-OC43 S2 Subunit Vaccine Fused with Nasal Immuno-Inducible Sequence Against Coronavirus Infection
by Hiraku Sasaki, Hiroki Ishikawa, Ayako Shigenaga, Yoshio Suzuki and Masayuki Iyoda
Curr. Issues Mol. Biol. 2025, 47(5), 355; https://doi.org/10.3390/cimb47050355 - 13 May 2025
Viewed by 49
Abstract
A partial sequence of an human coronavirus (HCoV)-OC43 S2 subunit that cross-reacts with the S2 subunit of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was fused with a nasal immuno-inducible sequence (NAIS), and the resulting complex was used for intranasal immunization of rabbits. [...] Read more.
A partial sequence of an human coronavirus (HCoV)-OC43 S2 subunit that cross-reacts with the S2 subunit of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was fused with a nasal immuno-inducible sequence (NAIS), and the resulting complex was used for intranasal immunization of rabbits. Crude serum from rabbits immunized with three doses showed an IgG titer > 1000 against the S2 subunits of HCoV-OC43 and SARS-CoV-2 and inhibited OC43 viral replication as a neutralizing antibody in vitro. Full article
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22 pages, 5867 KiB  
Article
Effect of 14-Week Supplementation of Highly Purified Policosanol (Raydel®) and a Sugar Cane Extract Powder (SCEP) on Dyslipidemia and Oxidative Variables in Hyperlipidemic Zebrafish: Insight into Liver, Kidney, and Brain Health
by Kyung-Hyun Cho, Ashutosh Bahuguna, Sang Hyuk Lee, Ji-Eun Kim, Yunki Lee and Cheolmin Jeon
Curr. Issues Mol. Biol. 2025, 47(5), 354; https://doi.org/10.3390/cimb47050354 - 13 May 2025
Viewed by 72
Abstract
The efficacy of Cuban sugarcane-extracted policosanol (Raydel®), a purified blend of eight long-chain aliphatic alcohols, was compared to copycat sugarcane-extract powder (SCEP) to assess their effects on dyslipidemia, oxidative stress, and vital organs of zebrafish under the influence of a high-cholesterol [...] Read more.
The efficacy of Cuban sugarcane-extracted policosanol (Raydel®), a purified blend of eight long-chain aliphatic alcohols, was compared to copycat sugarcane-extract powder (SCEP) to assess their effects on dyslipidemia, oxidative stress, and vital organs of zebrafish under the influence of a high-cholesterol diet (HCD). Zebrafish were fed with HCD (final 4%, w/w) or HCD infused with policosanol (PCO, final 1%, w/w) or SCEP (final 1%, w/w). Post 14-week consumption, blood and organs were harvested and processed for various biochemical, histological, and immunohistochemical (IHC) examinations, and fluorescent staining. Following 14-week consumption, the PCO-supplemented group exhibited higher zebrafish survival probability than the SCEP-supplemented group. Both PCO and SCEP substantially impacted the HCD-disrupted plasma lipid profile; however, PCO supplementation exhibited a significantly better effect than SCEP. Similarly, PCO supplementation significantly improved the blood glucose level, hepatic function biomarkers, and oxidative-antioxidant balance disturbed by HCD. PCO supplementation displayed a substantial inhibitory effect against HCD-induced fatty liver changes, nephromegaly, and cellular senescence. Likewise, PCO effectively protected the brain against HCD-induced apoptosis and accumulation of 4-hydroxynonenal (4-HNE); in contrast, SCEP supplementation showed almost no effect in reducing such adverse changes. The comparative findings between PCO and SCEP highlight the protective effects of PCO against HCD-induced oxidative stress and dyslipidemia via the enhancement of antioxidant markers, leading to protection of the liver, kidney, and brain, while SCEP failed to achieve similar outcomes. Full article
(This article belongs to the Section Molecular Pharmacology)
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16 pages, 1645 KiB  
Article
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 - 12 May 2025
Viewed by 189
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
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45 pages, 15230 KiB  
Article
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
Viewed by 138
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  
Brief 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
Viewed by 95
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
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16 pages, 1159 KiB  
Review
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
Viewed by 115
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  
Article
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 224
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, 1105 KiB  
Article
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 207
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
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23 pages, 1318 KiB  
Review
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 130
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  
Article
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 102
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  
Article
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 204
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  
Review
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 202
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  
Review
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 198
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
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15 pages, 4488 KiB  
Article
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
Viewed by 190
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  
Article
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 253
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
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10 pages, 6258 KiB  
Article
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 195
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  
Article
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 227
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
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14 pages, 10417 KiB  
Article
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 255
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  
Editorial
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 170
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  
Article
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
Viewed by 191
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  
Article
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
Viewed by 145
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  
Case 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 159
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
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