Current Molecular Medicine[JOURNAL]
Sun
200 papers
Analysis of Cytokine mRNA Expression During Zika Virus Infection In Mesocricetus auratus.
Mendes WRB, Melo KFL, Luna FCF … +5 more , Santos CRD, Franco ECDS, Filho AJM, Vasconcelos PFDC, Casseb SMM
Curr Mol Med · 2025 Apr · PMID 40325526 · Publisher ↗
BACKGROUND: The Orthoflavivirus zikaense (ZIKV), a member of the Flaviviridae family, has been associated with severe neurological issues, particularly microcephaly, due to its ability to infect neural progenitor cells....
BACKGROUND: The Orthoflavivirus zikaense (ZIKV), a member of the Flaviviridae family, has been associated with severe neurological issues, particularly microcephaly, due to its ability to infect neural progenitor cells. This study investigates the mRNA expression of cytokines involved in the inflammatory response during ZIKV infection in Mesocricetus auratus. The research aims to understand the immune response to ZIKV in the context of sexual transmission. METHODS: The study utilized hamsters of the species Mesocricetus auratus, divided into four groups: three infected with ZIKV and one control group. The animals were euthanized according to ethical guidelines, and renal tissues were collected. Total RNA was extracted and quantified, and both viral load and cytokine mRNA levels were measured using RT-qPCR. The study targeted cytokines such as TNF-A, RIG-I, RANTES, MDA5, IFN-A, and IFN-B. Statistical analysis was performed using Jamovi v 1.6. RESULTS: The study found that the viral load peaked between 3 and 5 days postinfection and then significantly decreased. The expression of cytokine mRNAs showed distinct patterns, with peaks and declines at various time points post-infection. These patterns differed between male and female subgroups. Pearson correlation analysis revealed negative correlations between mRNA expression and days post-infection in most groups. CONCLUSION: The study concludes that ZIKV infection in hamsters induces a robust inflammatory response in the kidneys, with dynamic cytokine expression profiles that could serve as markers for monitoring infection and related pathologies. Genderspecific immune responses highlight the complexity of ZIKV pathogenesis, suggesting potential therapeutic targets for Zika-related complications.
Hemolysis Analysis and Hemolysis-related MicroRNA Candidates for Serum/Plasma Samples.
He R, Zhou Y
Curr Mol Med · 2025 Apr · PMID 40296637 · Publisher ↗
Hemolysis is a major challenge in the screening and validation of serum or plasma miRNA biomarkers for human diseases. Over the past decade, numerous studies have focused on hemolysis detection at both the pre-analytical...
Hemolysis is a major challenge in the screening and validation of serum or plasma miRNA biomarkers for human diseases. Over the past decade, numerous studies have focused on hemolysis detection at both the pre-analytical and postanalytical stages to minimize bias in miRNA quantification. Both conventional and advanced hemolysis determination methods have played important roles in quality control in hemolysis assessment and risk prediction during the plasma or serum miRNA quantification process. This review discusses the advantages of these methods and provides an interactive summary of prior knowledge on hemolysissensitive miRNAs and their potential applications in disease diagnosis. Furthermore, the review highlights the advancements in machine learning technologies that enhance classifier predictions and hemolysis risk model evaluations, particularly during the post-analytical stage. Finally, it discusses the ongoing development, standardization, and potential applications of these approaches, which will contribute to a more comprehensive and interpretable framework for the discovery and validation of plasma or serum miRNA biomarkers.
Exercise Alleviates Atherosclerosis Through the Modulation of the NLRP3 Inflammasome.
Liu X, Hu S, Wang X … +1 more , Ding Y
Curr Mol Med · 2025 Apr · PMID 40289976 · Publisher ↗
Atherosclerosis (AS) is a chronic inflammatory disease closely associated with endothelial dysfunction and oxidative stress. The NOD-like receptor protein 3 (NLRP3) inflammasome, a key regulator of inflammatory responses...
Atherosclerosis (AS) is a chronic inflammatory disease closely associated with endothelial dysfunction and oxidative stress. The NOD-like receptor protein 3 (NLRP3) inflammasome, a key regulator of inflammatory responses, can exacerbate the progression of AS when activated. Growing evidence suggests that exercise, as a non-pharmacological intervention, can alleviate the progression of AS by modulating the activity of NLRP3 inflammasome. This review discusses how exercise influences the development of AS through the regulation of NLRP3 inflammasome and the underlying molecular mechanism. This study introduces the structure and activation mechanisms of NLRP3 inflammasome, as well as its role in AS. And summarizes how exercise can ameliorate endothelial dysfunction, regulate lipid metabolism, and suppress oxidative stress and inflammation by affecting the expression and activity of NLRP3 inflammasome, thereby exerting a beneficial impact on AS. Additionally, we explore the effects of exercise on the downstream inflammatory cytokines of NLRP3 inflammasome and how this regulation could help to slow the progression of AS. These findings underscore the therapeutic relevance of exercise in the prevention and treatment of AS. It provides new insights into the role of exercise interventions in the management of AS and lays a theoretical foundation for the development of innovative treatment strategies for cardiovascular disease. Given that the NLRP3 inflammatome plays an important role in the pathogenesis and treatment of AS, exercise therapy strategies targeting the NLRP3 inflammatome will help promote the development of precision medicine for AS.
Prognostic Value and Immunological Role of CBX7 in Lung Adenocarcinoma.
Yang L, Huang Y, Mo W … +2 more , Wu L, Wen C
Curr Mol Med · 2025 Apr · PMID 40277108 · Publisher ↗
BACKGROUND: Chromobox 7 (CBX7) has been implicated in the progression of various malignant tumors, but its clinical relevance in lung adenocarcinoma (LUAD) remains poorly understood. This study aimed to investigate the e...
BACKGROUND: Chromobox 7 (CBX7) has been implicated in the progression of various malignant tumors, but its clinical relevance in lung adenocarcinoma (LUAD) remains poorly understood. This study aimed to investigate the expression, prognostic value, biological functions, and immunological role of CBX7 in LUAD. METHODS: CBX7 expression in LUAD and adjacent normal tissues was analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Kaplan-Meier curves and Cox risk regression evaluated prognostic significance. Various algorithms assessed the correlation between CBX7 and immune microenvironment. The expression of CBX7 in LUAD tissues was detected by RT-qPCR, western blotting, and immunohistochemistry. The function of CBX7 in LUAD was further investigated by in vitro and in vivo experiments. RESULTS: CBX7 expression significantly downregulated LUAD, which was associated with aberrant DNA methylation. Decreased CBX7 expression correlated with advanced tumor stage and poor prognosis. Notably, CBX7 is associated with immune cell infiltration and immune checkpoints, highlighting its potential role in guiding immunotherapy. Functional experiments demonstrated that CBX7 overexpression suppressed the malignant phenotype of LUAD cells, while CBX7 knockdown promoted tumor progression. CONCLUSION: We conducted a systematic analysis of the diagnostic, prognostic, and immunological significance of CBX7 in LUAD, and found that it might serve as a diagnostic marker and therapeutic target in the future.
Ginsenoside Rg1 Attenuates Muscle Atrophy in Hyperglycemic Conditions, Inactivity and Protein Deprivation Models via AKT/mTOR Pathway Activation.
He X, Li Y, Chen J … +4 more , Zhang L, Huang Y, Zhou Y, Li J
Curr Mol Med · 2025 Apr · PMID 40277061 · Publisher ↗
BACKGROUND: Muscle atrophy, a debilitating condition prevalent in diabetes and extended periods of immobilization, lacks robust therapeutic strategies. This investigation examines ginsenoside Rg1's therapeutic potential...
BACKGROUND: Muscle atrophy, a debilitating condition prevalent in diabetes and extended periods of immobilization, lacks robust therapeutic strategies. This investigation examines ginsenoside Rg1's therapeutic potential in counteracting muscle atrophy under hyperglycemic conditions and in experimental models of immobilization and dietary protein restriction. METHODS: C2C12 murine myoblasts were cultured under variable glucose concentrations and treated with or without Rg1. Multiple cellular parameters were evaluated, including cell viability, apoptotic indices, cell cycle distribution, and protein synthesis rates. The activation status of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling cascade and expression of atrophy-related markers were quantified using qRT-PCR and Western blot analyses. In parallel animal studies, rats were subjected to either immobilization or protein restriction protocols, with or without Rg1 administration. Muscle function, mass, and relevant biomarkers were evaluated. RESULTS: Hyperglycemic conditions significantly compromised C2C12 myoblast viability, triggered apoptotic pathways, and disrupted normal cell cycle progression. Rg1 administration effectively attenuated these detrimental effects through enhanced AKT/mTOR pathway activation, upregulation of Myogenin (MyoG) expression, and suppression of atrophy-associated markers. In the rat models, Rg1 supplementation significantly ameliorated muscle deterioration, maintaining muscle mass, contractile force, and exercise tolerance, while simultaneously modulating atrophy signaling pathways and attenuating inflammatory responses. The protective effects of Rg1 were abrogated after the co-treatment with an AKT inhibitor. CONCLUSION: Ginsenoside Rg1 exhibits significant protective properties against muscle atrophy under hyperglycemic conditions and in experimental models of immobilization and protein restriction, primarily mediated through activation of the AKT/mTOR signaling pathway. These findings establish Rg1 as a promising therapeutic candidate for the treatment of muscle atrophy.
Dihydroorotate Dehydrogenase as a Modulator of Ferroptosis in Myocardial Ischemia-reperfusion Injury.
Alip M, Guo Z, Yang S … +6 more , Wuji A, Yasen A, Han B, Muaibati M, Wu H, Cui X
Curr Mol Med · 2026 · PMID 40277060 · Publisher ↗
INTRODUCTION: Ferroptosis is increasingly acknowledged as a pivotal contributor to myocardial cell injury in ischemia-reperfusion (I/R). As a central enzyme in the pyrimidine synthesis pathway, dihydroorotate dehydrogena...
INTRODUCTION: Ferroptosis is increasingly acknowledged as a pivotal contributor to myocardial cell injury in ischemia-reperfusion (I/R). As a central enzyme in the pyrimidine synthesis pathway, dihydroorotate dehydrogenase (DHODH) is implicated in maintaining redox homeostasis and is thought to act as a protective agent against ferroptosis. Despite this association, the specific contributions of DHODH to myocardial ischemia-reperfusion injury (MIRI) and its cardioprotective potential remain inadequately elucidated. AIM: This study aimed to delineate the role of DHODH in MIRI and assess its capacity to modulate ferroptosis in cardiomyocytes. METHODS: We utilized AC16 cardiomyocytes to establish an in vitro MIRI model to investigate the role of DHODH in ferroptosis. We quantitatively analyzed DHODH expression during I/R injury, along with its distribution in cytoplasmic and mitochondrial compartments. Cells pretreated with dihydroorotate (DHO) and orotate (OA)-the substrate and product of DHODH, respectively-provided a basis for assessing their susceptibility to ferroptosis. By employing siRNA to suppress DHODH expression, we delved into the underlying mechanisms of DHODH's protective role against I/Rinduced ferroptosis, focusing on oxidative stress and mitochondrial dysfunction. RESULTS AND DISCUSSION: Our findings reveal a significant induction of DHODH expression during ferroptosis in the AC16 I/R model. DHO pretreatment conferred resistance to ferroptosis, while OA pretreatment rendered cells more susceptible. Notably, DHODH silencing aggravated ferroptosis indicators, mainly through increased oxidative stress and mitochondrial dysfunction. CONCLUSION: DHODH emerges as a key modulator of ferroptosis in the context of MIRI, offering protection predominantly through its antioxidative functions and maintenance of mitochondrial integrity.
Protease-activated Receptor 2 Promotes Crohn's Disease-Associated Colonic Fibrosis through Fibroblast Activation.
Wang Z, Liu B, Chu C … +1 more , Liu F
Curr Mol Med · 2025 · PMID 40265432 · Publisher ↗
AIMS: To clarify the roles of PAR-2 (protease-activated receptor 2) in Crohn's disease-associated colonic fibrosis. BACKGROUND: G protein-coupled receptor, termed PAR-2, is triggered after serine proteases. Through activ...
AIMS: To clarify the roles of PAR-2 (protease-activated receptor 2) in Crohn's disease-associated colonic fibrosis. BACKGROUND: G protein-coupled receptor, termed PAR-2, is triggered after serine proteases. Through activating genes encoding extracellular matrix proteins and proinflammatory cytokines, PAR-2 triggering promotes inflammatory / pro-fibrotic pathways. Although PAR-2 is highly expressed within the digestive system, its significance within colonic fibrosis (CF) has not yet been probed. OBJECTIVE: To assess the roles and mechanisms of PAR-2 in Crohn's diseaseassociated colonic fibrosis. METHODS: PAR-2 expression was assessed variably in the colon of human and model mice. Immunofluorescence assay was used to analyze the phenotypic changes of fibroblasts after PAR-2 activation in the lamina propria. In in vitro assays, we explored the roles of PAR-2 in CCD-18Co fibroblasts treated with PAR-2 inhibitor ENMD-1068 and PAR-2 agonist SLIGRL-NH2. RESULTS: PAR-2 was highly expressed in the subepithelial layer surrounding colonic crypts of CD patients or murine fibrosis cohort. Colonic PAR-2 expression was consistent with collagen deposition. Decreasing PAR-2 in experimental colon fibrosis caused a decrease in the amount of colonic collagen and histological fibrosis, followed by a reduction in colonic fibroblast activation. PAR-2 activation enhanced CF by showing a profibrogenic phenotype and collagen synthesis within CCD-18Co fibroblasts. CONCLUSION: Our results show that PAR-2 activation could upregulate extracellular matrix (ECM) proteomic levels, encourage CF, and cause a pro-fibrogenic phenotype within human colonic myofibroblasts.
Inhibition of S100A12 Attenuates LPS-induced Endothelial Barrier Dysfunction in HPMECs through the JAK2/STAT3 Signaling Pathway.
Shen Y, Ye X, Jiang L … +4 more , Li H, Zhang Y, Wang W, Mao H
Curr Mol Med · 2026 · PMID 40248931 · Publisher ↗
BACKGROUND: The calcium-binding protein S100A12 plays a pivotal role in the progression of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, the underlying mechanisms are yet to be fully el...
BACKGROUND: The calcium-binding protein S100A12 plays a pivotal role in the progression of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, the underlying mechanisms are yet to be fully elucidated. OBJECTIVE: This study aimed to investigate the role of S100A12 in LPS-induced injury of human pulmonary microvascular endothelial cells (HPMECs) and its molecular regulatory mechanism. METHODS: An in vitro model of ALI/ARDS was established by lipopolysaccharide (LPS)-induced HPMECs. CCK-8, flow cytometry assay, and ELISA were used to detect the cell viability, apoptosis, and inflammation. The integrity of the endothelial barrier was assessed by tube formation assay and VE-cadherin and occludin protein levels. The molecular mechanism of S100A12 was analyzed by transcriptomics and validated using qRT-PCR and western blotting analyses. RESULTS: S100A12 expression was significantly elevated in LPS-stimulated HPMECs, and S100A12 knockdown alleviated LPS-induced apoptosis, inflammation, and endothelial barrier dysfunction in HPMECs. Transcriptomic analysis revealed the potential gene network mapping regulated by LPS stimulation and S100A12 knockdown. Differentially expressed genes were significantly enriched in the JAK2/STAT3 signaling pathway as verified by western blotting analysis. DISCUSSION: In summary, our findings demonstrate that S100A12 promotes LPS-induced pulmonary endothelial barrier dysfunction primarily through activation of the JAK2/STAT3 signaling pathway. This reveals a previously uncharacterized mechanism for S100A12 in ALI/ARDS pathogenesis and positions it as a potential therapeutic target for attenuating lung endothelial injury. CONCLUSION: Our results suggested S100A12 to be significantly upregulated in LPS-induced HPMECs; inhibiting S100A12 can alleviate endothelial cell barrier dysfunction through the JAK2/STAT3 signaling pathway and thereby improve LPS-induced HPMECs injury.
Metabolomic Profiling Reveals Distinct Pathways in Degenerated and Non-degenerated Rotator Cuff Tears: Implications for Pathogenesis and Treatment.
Bulbul F, Koc E, Fidan BB … +6 more , Kaplan O, Ruzgar H, Bilge O, Ozer M, Celebier M, Korkusuz F
Curr Mol Med · 2026 · PMID 40197183 · Publisher ↗
BACKGROUND: Tissue metabolomics is a promising technology for evaluating in situ changes in disease pathogenesis. It addresses a significant knowledge gap in the study of both degenerated and non-degenerated supraspinatu...
BACKGROUND: Tissue metabolomics is a promising technology for evaluating in situ changes in disease pathogenesis. It addresses a significant knowledge gap in the study of both degenerated and non-degenerated supraspinatus (SSp) tendons. This study analyzed the metabolomic profiles associated with rotator cuff tears (RCTs). PURPOSE: RCTs cause loss of function and shoulder pain, with the SSp muscle being the most frequently affected. Inflammation and complex metabolic changes may play roles in its etiology. Evaluation of the metabolomic differences between the degenerated and non-degenerated SSp tissues of RCT patients was aimed. METHODS: A cross-sectional study of 14 patients with RCTs, diagnosed through physical examination and magnetic resonance imaging, was conducted. Degenerate and non-degenerate SSp tissue debris were collected during arthroscopy. Untargeted metabolomic analysis of these samples was performed using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-ToF-MS). Metabolic peaks were identified, matched, and normalized before further analysis. Partial least squaresdiscriminant analysis (PLS-DA), heatmap generation, unsupervised volcano plots, and fold-change analyses were conducted. A putative metabolite list was subsequently compiled to elucidate pathways of degeneration. These metabolites were matched with metabolic pathways using the RaMP-DB metabolite set library. RESULTS: The tyrosine metabolism (p=4.93 x10), ferroptosis (p=1.25 x10), steroidogenesis (p=9.89 x10), and cholesterol biosynthesis (p=3.05 x10) were altered in the degenerated RCTs. DISCUSSION: The observed alterations in tyrosine metabolism, ferroptosis, steroidogenesis, and lipid-related pathways highlight the multifactorial metabolic nature of rotator cuff degeneration. These pathway-specific changes suggest a close interplay between oxidative stress, inflammatory signaling, and hormonal regulation in the progression of tendon degeneration. The identified metabolomic signatures may provide mechanistic insight into tissue degeneration and offer a foundation for the development of targeted and personalized therapeutic strategies in rotator cuff tear management. CONCLUSION: These findings suggest that metabolomic alterations may be associated with the development of RCTs, with changes in tyrosine metabolism, ferroptosis, and lipid metabolism potentially contributing to muscle degeneration and inflammation. Identified disruptions in steroidogenesis provide new insights into the role of hormonal factors in RCT development. Understanding these metabolic pathways is clinically relevant in sports medicine, as it enables targeted therapies and personalized treatment strategies, ultimately enhancing recovery and improving outcomes for athletes.
Analysis of Alternative Splicing Events in Melanoma and their Implications for Prognosis.
Deng H, Huang X, Zhang J … +6 more , Xu X, Wang J, Liu L, Yu Y, Feng J, He Y
Curr Mol Med · 2025 Apr · PMID 40197182 · Publisher ↗
INTRODUCTION: Alternative splicing (AS) events significantly affect melanoma progression. Therefore, understanding their effect on prognosis is important for developing new treatments. METHODS: Univariate Cox regression...
INTRODUCTION: Alternative splicing (AS) events significantly affect melanoma progression. Therefore, understanding their effect on prognosis is important for developing new treatments. METHODS: Univariate Cox regression analysis and LASSO regression were carried out to identify key AS events, build an AS risk model, and classify sample risk levels. Pearson correlation analysis was also performed to analyze the relationship between AS events and RNA-binding protein (RBP) genes or indicators of immune infiltration. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using gene expression data from patients with varying risk levels. Univariate and multivariable Cox regression analyses were also carried out to examine the association between immune cell infiltration and prognosis. RESULTS: A total of 41446 AS events were identified; among them, 446 AS events were identified as significantly associated with melanoma prognosis. An AS risk model for prognosis was established using seven key AS events. A close correlation was found between 137 AS events and 1037 RBP genes, suggesting that these genes may participate in the regulation of AS events. KEGG enrichment analysis revealed that the genes involved in AS were closely associated with immune system functions, which may explain why AS events affect the prognosis of melanoma. Finally, by combining the AS risk score and clinical indicators, we developed a nomogram model that could effectively predict melanoma prognosis. CONCLUSION: This analysis of AS events and regulation may aid in developing novel prognostic biomarkers and therapeutic targets for melanoma.
Enhancement of Platinum-based Drug Sensitivity in Ovarian Cancer Cells Through Hyperthermia-induced Activation of the TGF-β1/β-Catenin Signaling Pathway.
Lv X, Wu W, Huang G … +3 more , Yao X, Zeng S, Wang Y
Curr Mol Med · 2026 · PMID 40197181 · Publisher ↗
BACKGROUND: Platinum-based drugs like cisplatin are key in treating ovarian cancer, but resistance frequently leads to treatment failure. The TGF-β1/β- catenin signaling pathway has been implicated in tumor resistance. T...
BACKGROUND: Platinum-based drugs like cisplatin are key in treating ovarian cancer, but resistance frequently leads to treatment failure. The TGF-β1/β- catenin signaling pathway has been implicated in tumor resistance. This study investigates whether hyperthermiaenhances ovarian cancer cell sensitivity to platinum-based drugs by activating the TGF-β1/β-catenin pathway. METHODS: and models of ovarian cancer were treated with hyperthermia and cisplatin. Changes in TGF-β1 and β -catenin expression were measured using Western blotting, qPCR, immunohistochemistry, and cell viability assays to determine the impact of hyperthermia on drug sensitivity. RESULTS AND DISCUSSION: Hyperthermia significantly reduced TGF-β1 and β-catenin expression in ovarian cancer cells and tumor tissues, suppressing the pathway. This led to increased cisplatin sensitivity and higher apoptosis rates , while in vivo, tumor growth was significantly suppressed, and cisplatin's antitumor effects were enhanced. CONCLUSION: Hyperthermia boosts the effectiveness of platinum-based drugs in ovarian cancer by suppressing the TGF-β1/β-catenin pathway, presenting a potential strategy to overcome chemoresistance and improve patient outcomes.
Bone Marrow Mesenchymal Stem Cell Senescence in the Development of Osteoporosis: Mechanisms, Interventions, and Future Directions.
Li C, Li B, Zhang J … +4 more , Liu K, Du G, Guo C, Yang Z
Curr Mol Med · 2025 Mar · PMID 40151080 · Publisher ↗
Osteoporosis, a significant age-related disease, is marked by diminished bone density and an elevated risk of fractures, representing a considerable global health challenge. Bone marrow mesenchymal stem cells (BMSCs) are...
Osteoporosis, a significant age-related disease, is marked by diminished bone density and an elevated risk of fractures, representing a considerable global health challenge. Bone marrow mesenchymal stem cells (BMSCs) are essential in maintaining bone integrity through their differentiation into osteoblasts, which are crucial for bone formation. Nevertheless, the aging of BMSCs diminishes their regenerative abilities and intensifies inflammation, thereby playing a critical role in osteoporosis pathogenesis. This review explores the intricate mechanisms of BMSC senescence and its influence on osteoporosis, detailing cellular and molecular markers, such as oxidative stress, the senescence-associated secretory phenotype (SASP), and pivotal signaling pathways, including P53, PI3K/mTOR, and autophagy. We assess current interventions aimed at reducing BMSC senescence, with an emphasis on pharmacological methods like melatonin and antioxidants, alongside nonpharmacological strategies, such as exercise and dietary supplementation with omega-3 fatty acids. Furthermore, the challenges and limitations of translating these strategies into clinical applications are addressed, highlighting the necessity for personalized medicine to accommodate treatment outcome variability. Future research directions should focus on emerging therapeutic targets and novel interventions, such as gene editing technologies and advanced tissue engineering techniques. By integrating these strategies, this review endeavors to enhance the understanding and treatment of osteoporosis, emphasizing the critical need to target BMSC senescence to develop effective therapies.
High Glycolysis and Lipid Metabolism Status Predicts Poor Prognosis in Colorectal Cancer Patients.
Li M, Yue M, Chen Y … +1 more , Zhao G
Curr Mol Med · 2026 · PMID 40143685 · Publisher ↗
BACKGROUND: The prognosis of patients with stage III colorectal cancer (CRC) shows significant variations. The purpose of this study was to investigate the role of key regulatory proteins in glycolysis and lipid metaboli...
BACKGROUND: The prognosis of patients with stage III colorectal cancer (CRC) shows significant variations. The purpose of this study was to investigate the role of key regulatory proteins in glycolysis and lipid metabolism for the prognostic evaluation of stage III CRC patients. METHODS: Utilizing the Cancer Genome Atlas (TCGA) database, we analyzed the expression of various key regulatory genes in glycolysis and lipid metabolism pathways in CRC, as well as the relationship between gene expression levels and overall survival.. We selected the top two key genes exhibiting differential expression patterns in glycolysis and lipid metabolism, namely, glucose transporter type 1 (GLUT1), pyruvate kinase M2 (PKM2), fatty acid synthase (FASN), and stearoyl-CoA desaturase 1 (SCD1), as targets for subsequent exploration. We analyzed the effects of GLUT1, PKM2, FASN, and SCD1 on the proliferation, migration, and drug sensitivity of CRC cells in vitro. These proteins were detected by immunohistochemistry (IHC) in the clinical tissues of stage III CRC patients. Based on the intensity of IHC staining for GLUT1, PKM2, FASN and SCD1, the cumulative score from these 4 target proteins for each sample was calculated (score range from 0 to 8). The relationships between high (scores of 6-8) or low (scores of 0-5) expression of glycolysis and lipid metabolism molecules and the clinicopathological characteristics, and survival of patients were analyzed. RESULTS: The expression disparities of the GLUT1, PKM2, FASN, and SCD1 genes were the most prominent between tumor and normal tissues. Overexpression of GLUT1, PKM2, FASN, or SCD1 significantly promoted CRC cell growth and migration, as evidenced by CCK-8, colony formation, and Transwell assays. Exogenous introduction of GLUT1, PKM2, FASN, or SCD1 increased oxaliplatin IC values, enhanced cell survival, and reduced early apoptosis in CRC cells exposed to oxaliplatin. High glycolysis and lipid metabolism status were associated with poor tumor differentiation, vascular or nerve invasion, and shorter overall survival. The status of glycolysis and lipid metabolism was an independent prognostic factor for stage III CRC patients. DISCUSSION: Based on IHC staining of GLUT1, PKM2, FASN, and SCD1, we established a protein-based scoring system to classify stage III CRC patients into high or low glycolipid metabolism groups. This scoring system provides a practical and objective method for prognostic assessment, offering potential guidance for treatment strategies in stage III CRC patients. CONCLUSION: High glycolysis and lipid metabolism status are correlated with a poor prognosis in patients with stage III colorectal cancer.
Advancing Precision Oncology: Overcoming Treatment Resistance for Personalized Cancer Care.
Singh D
Curr Mol Med · 2025 · PMID 40077818 · Publisher ↗
Abstract loading — click title to view on PubMed.
Potential Effects of Opium on Pro-inflammatory Cytokines in Coronary Artery Disease by Interfering with Anti-inflammatory Drugs.
Momeni-Moghaddam MA, Asadikaram G, Masoumi M … +4 more , Arababadi MK, Sadeghi E, Khaksari M, Akbari H
Curr Mol Med · 2026 · PMID 40070058 · Publisher ↗
BACKGROUND: Opium is one of the factors that may interfere with coronary artery disease (CAD). This study aimed to investigate the role of opium in certain pro-inflammatory and anti-inflammatory cytokines in CAD patients...
BACKGROUND: Opium is one of the factors that may interfere with coronary artery disease (CAD). This study aimed to investigate the role of opium in certain pro-inflammatory and anti-inflammatory cytokines in CAD patients with and without opium dependence on regular prescription medicines. METHODS: Seventy-seven patients with suspected CAD were selected as candidates for coronary angiography in this case-control study. They were categorized into three groups:1) CAD opiumaddicted (CAD+OA, n=30); 2) CAD non-opium-addicted (CAD, n=30); and 3) non-opium-addicted with no CAD individuals as a control group (Ctrl, n=17). Routine medications, including aspirin, atorvastatin, bisoprolol, valsartan, losartan, clopidogrel, metoprolol, isosorbide, trinitrate glyceryl, captopril, and carvedilol, were administered to these patients. ELISA was performed to quantify plasma levels of interleukin-23 (IL-23), IL-17, IL-1β, transforming growth factor beta (TGF-β), and IL-10. RESULTS: A significantly higher level of IL-23 was found in the CAD+OA group than in the CAD and control groups. In addition, in the CAD+OA group, the mean difference in TGF-β levels was significantly lower than that in CAD patients, whereas no significant difference was found between the Ctrl group and the CAD+OA and CAD groups. No significant differences were observed in the mean levels of IL-17, IL-1β, or IL-10 among the groups. DISCUSSION: Considering the significant increase in plasma levels of IL-23, a pro-inflammatory cytokine, in the CAD+OA group compared with the other two groups, opium may play an important role in increasing inflammation. Also, given the important role of IL-23 in the differentiation of Th17 cells (producers of IL-17), the lack of increase in IL-17 and IL-1β in the three groups, the decrease in TGF-β levels in the CAD+OA group compared with the CAD group, and the fact that CAD and CAD+OA patients were treated with anti-inflammatory drugs, it can be assumed that these drugs modulate cytokine expression. CONCLUSION: Opium was found to contribute to the induction of inflammation by interfering with cardiovascular medications, resulting in deterioration of CAD complications. Additionally, certain medications, including aspirin, glyceryl trinitrate, atorvastatin, and clopidogrel, played a significant role in regulating the expression of cytokines.
Proteomic Analysis of Molecular Mechanisms Involved in TGF-β-Induced Epithelial-Mesenchymal Transition in Human Lung Adenocarcinoma A549 Cells.
Tang WH, Wang DM, Zhan Z … +3 more , Kang DH, Wan T, Liu ZF
Curr Mol Med · 2025 · PMID 40059417 · Publisher ↗
OBJECTIVE: This study aimed to examine the molecular mechanisms involved in transforming growth factor-β (TGF-β)-induced epithelial-mesenchymal transition (EMT) in human lung adenocarcinoma (LUAD) A549 cells. METHODS: Pr...
OBJECTIVE: This study aimed to examine the molecular mechanisms involved in transforming growth factor-β (TGF-β)-induced epithelial-mesenchymal transition (EMT) in human lung adenocarcinoma (LUAD) A549 cells. METHODS: Proteins were extracted from cultured human LUAD A549 cells cultured under two conditions: untreated and treated with TGF-β (5 ng/ml) for 48 hours. The expression levels of EMT-related proteins, including E-cadherin, Vimentin, and α- smooth muscle actin, were assessed using western blotting. Proteomic analysis was performed using isobaric tags for relative and absolute quantification combined with two-dimensional liquid chromatography-tandem mass spectrometry. Differentially expressed proteins were subjected to bioinformatics analysis, including functional annotation and interaction network studies. RESULTS: A total of 122 proteins were identified as differentially expressed between the untreated and TGF-β-treated A549 cells. Of these, 55 proteins were upregulated, while 67 were downregulated following TGF-β treatment. Bioinformatics and interaction network analyses highlighted six proteins-GAPDH, TP53, MAPK1, IGF1, SRC, and MYC-as being closely associated with the EMT in human LUAD. CONCLUSION: This study provides new insights into the processes of invasion and metastasis in LUAD by examining the molecular mechanisms underlying TGF-β- induced EMT in A549 cells.
Promotes the Process of Diabetic Nephropathy by Promoting the Expression of .
Zhao P, Deng T, Zeng J
Curr Mol Med · 2026 · PMID 40045860 · Publisher ↗
BACKGROUND: The analysis of diabetic nephropathy (DN)-related gene dataset demonstrated that C-X-C motif chemokine ligand 3 (CXCL3) is highly expressed in DN. Exploring the impact of CXCL3 in the course of DN is the core...
BACKGROUND: The analysis of diabetic nephropathy (DN)-related gene dataset demonstrated that C-X-C motif chemokine ligand 3 (CXCL3) is highly expressed in DN. Exploring the impact of CXCL3 in the course of DN is the core goal of this study. METHODS: The cell model used in this study was CIHP-1 cells induced by high glucose (HG). qRT-PCR and western blot analysis were carried out to determine the expression difference of CXCL3. After down-regulating the CXCL3 level, we analyzed HG-induced CIHP-1 cell viability by MTT assay, proliferation by EdU staining, apoptosis by flow cytometry, and changes in related protein expression by western blot. In order to analyze the possible regulatory relationship between endothelial cellspecific molecule 1 (ESM-1) and CXCL3 in DN, we constructed an over-expressed ESM-1 plasmid and carried out a rescue experiment. RESULTS: CXCL3 and ESM-1 were highly expressed in HG-induced podocytes (p<0.05). Silenced CXCL3 (siCXCL3) increased the viability and proliferation of CIHP- 1 cells induced by HG, reduced the proportion of apoptosis, and produced corresponding protein changes (p<0.01). After the overexpression of ESM-1, the effects of siCXCL3 were partially offset (p<0.05). DISCUSSION: This study reveals that ESM-1 exacerbates HG-induced podocyte injury by promoting CXCL3 expression, identifying a novel ESM-1/CXCL3 regulatory axis in DN progression. While the findings are derived from a specific cell model and the precise molecular mechanism requires further elucidation, consistent rescue experiments support this functional linkage. These results suggest that targeting the ESM-1/CXCL3 pathway may mitigate podocyte damage in DN, offering a potential therapeutic direction. Future studies should validate this axis in vivo and explore its clinical relevance. CONCLUSION: In this study, ESM-1 increased HG-induced podocyte damage by promoting CXCL3 expression.
2-DG Promotes the Proliferation, Differentiation, Migration, and Resistance to Oxidative Stress of Mesenchymal Stem Cells through Hippo Signaling.
Dong L, Li L
Curr Mol Med · 2025 · PMID 40012386 · Publisher ↗
BACKGROUND: Hippo signaling regulates the behavior and fate of mesenchymal stem cells (MSCs), which are crucial for the repair and cure of acute respiratory distress syndrome (ARDS). However, whether 2-deoxy-D-glucose (2...
BACKGROUND: Hippo signaling regulates the behavior and fate of mesenchymal stem cells (MSCs), which are crucial for the repair and cure of acute respiratory distress syndrome (ARDS). However, whether 2-deoxy-D-glucose (2-DG), a specific activator of Hippo signaling, would further enhance the reparative effect of MSCs in ARDS remains unclarified. OBJECTIVE: This study aimed to determine whether 2-DG could promote the proliferation, differentiation, migration, and resistance to oxidative stress of mouse bone marrow-derived MSCs (mBMSCs). METHODS: mBMSCs were isolated from C57BL/6 mice and differentiated into alveolar type II epithelial (ATII) cells by noncontact coculture. The specific activator and inhibitor 2-DG and 4-[(5,10-dimethyl-6-Oxo-6,10-dihydro-5h-pyrimido[5,4-B]thieno[3,2- E][1,4]diazepin-2-Yl)amino]benzenesulfonamide (XMU-MP-1) were used to activate and inhibit Hippo signaling, respectively. Oxidative stress-induced injuries were induced by HO treatment. RESULTS: We observed that 2-DG activated Hippo signaling and promoted mBMSC proliferation in a dose-dependent manner. 2-DG also promoted the differentiation of mBMSCs into ATII cells and enhanced not only the horizontal and vertical migration of mBMSCs but also mBMSC homing to injured lung tissue. HO treatment inhibited Hippo signaling and reduced the viability of mBMSCs by decreasing the Bcl-2/Bax ratio, but 2-DG activated Hippo signaling and conferred mBMSCs with resistance to oxidative stress by increasing the Bcl-2/Bax ratio. However, XMU-MP-1 suppressed these effects to some extent. CONCLUSION: Through Hippo signaling, 2-DG promoted the proliferation, migration, differentiation, and resistance to oxidative stress of mBMSCs, suggesting a novel strategy for enhancing the reparative effects of MSCs in ARDS.
From Reactive Hyperplasia to Neoplastic Changes: Histopathological Insights into Lymphadenopathy.
Khan N, Abbas FF, Kamil S … +5 more , Shahid R, Shah ST, Rizvi A, Kamil N, Ali R
Curr Mol Med · 2025 · PMID 39988781 · Publisher ↗
BACKGROUND: Inflammation, infection, autoimmune diseases, or malignancy can cause the abnormal proliferation of lymphocytes; therefore, clinicians should always take detailed history and physical examination to screen th...
BACKGROUND: Inflammation, infection, autoimmune diseases, or malignancy can cause the abnormal proliferation of lymphocytes; therefore, clinicians should always take detailed history and physical examination to screen the patient for lymphadenopathy. OBJECTIVES: The aim and objective of the current study was to assess the pattern of diseases causing lymphadenopathies in the Pakistani Population. METHODOLOGY: The current study was a cross-sectional study. Data were obtained from existing patient records from Dow Diagnostic Research and Reference Laboratory [DDRRL]-Dow University of Health Sciences [DUHS] from Jan 2020 to Dec 2022. Patients undergoing chemotherapy and biopsies with poor preservation and inconclusive diagnosis were excluded from the study, while patients of any age, gender, and various sites of lymphadenopathy were included in this study. Ethical approval was obtained from the ethical Review Board [IRB] of Dow University of Health Sciences [DUHS]. RESULTS: A total of 675 FNAC and lymph node biopsies of lymph nodes were obtained. Age, location, and gender were taken into consideration when analyzing the lymph node biopsy materials of these patients. There were 200 [29.62%] males and 475 [70.37%] females. The age range of the patients was 1 year to 80 years, and the mean [SD] age of the patients was 33.76 ± 17.54 years. CONCLUSION: In the current study, we aim to provide guidance to the clinician on initial diagnostic laboratory testing, imaging, and the potential need for biopsy by evaluating the pattern of diseases causing lymphadenopathy in our population.
The Molecular Mechanism of a Complex1-induced Apoptosis in Cancer Cells of the Esophagus.
Liu ZQ, Luo JR, Yao X … +4 more , Wang ZH, Hao SY, Li MX, Zhang H
Curr Mol Med · 2026 · PMID 39981670 · Publisher ↗
BACKGROUND: Esophageal Cancer (EC) is a commonly occurring cancer of the digestive tract. The bismuth compounds from thiosemicarbazones have been observed to be active against cancer cells. However, a synthetic nine-coor...
BACKGROUND: Esophageal Cancer (EC) is a commonly occurring cancer of the digestive tract. The bismuth compounds from thiosemicarbazones have been observed to be active against cancer cells. However, a synthetic nine-coordinate bismuth (III) complex (complex 1) has never been assessed so far for its anticancer in the esophageal squamous cell carcinoma cell line (EC109). OBJECTIVES: Esophageal Cancer (EC) is a commonly occurring cancer of the digestive tract. The bismuth compounds from thiosemicarbazones have been observed to be active against cancer cells. This study aimed to investigate the apoptosis effect of a complex1 in the EC109 cells. METHODS: EC109 cells were treated with complex1. The MTT assay was employed to assess the viability of EC109 cells; the changes in apoptotic and morphological characteristics, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP) were examined. The expression levels of proteins associated with apoptosis were assessed using western blotting. RESULTS: Complex1 was found to inhibit the growth of EC109 cells, exhibiting an IC50 of 0.654 μM through apoptosis depends upon complexation with bismuth(III). In addition, cells exposed to complex1 exhibited a significant increase in the level of intracellular ROS through the suppression of the antioxidant system and caused a reduction in mitochondrial membrane potential(MMP). Co-treatment with N-acetyl-Lcysteine( NAC), an antioxidant agent prevented accumulation of ROS and cell death. Complex1 also led to enhanced Bax expression, and reduced Bcl-2 expression in EC109 cells, thereby enhancing caspase-3/9 activity. DISCUSSION: This study reported the first use of Complex 1 for treating EC109 cells and demonstrated its superior anticancer activity. Complex 1 triggered apoptosis by significantly increasing reactive oxygen species (ROS) levels. The mechanism involved the downregulation of Bcl-2 and the upregulation of Bax, which resulted in an elevated Bax/Bcl-2 ratio, mitochondrial membrane potential (MMP) disruption, and activation of the caspase cascades. These findings confirmed that mitochondrialmediated apoptosis is the primary pathway for the anticancer effects of Complex 1. CONCLUSION: Our study confirmed that complex1 induced apoptosis via enhancing the generation of ROS along with a decline in levels of antioxidant enzymes, subsequently causing MMP loss.
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