Current Molecular Medicine[JOURNAL]
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200 papers
A Novel Combined Therapeutic Approach to Endometriosis: Exosomes Derived from Human Wharton's Jelly Mesenchymal Stem Cells and Etanercept.
Mahdavi R, Dayer D, Amari A … +3 more , Jalili Z, Ghafourian M, Farzaneh M
Curr Mol Med · 2025 Sep · PMID 40993922 · Publisher ↗
INTRODUCTION: Endometriosis is a chronic disorder characterized by abnormal endometrial tissue growth. This study evaluates a novel combination immunomodulatory treatment involving etanercept (ETN) and exosomes derived f...
INTRODUCTION: Endometriosis is a chronic disorder characterized by abnormal endometrial tissue growth. This study evaluates a novel combination immunomodulatory treatment involving etanercept (ETN) and exosomes derived from human Wharton's jelly mesenchymal stem cells (hWJMSC-Exo) as a promising alternative to conventional therapies for modulating inflammation in endometriosis. METHODS: Endometrial stromal cells were isolated by enzymatic digestion of eutopic (EuESCs, N = 6) and ectopic (EESCs, N = 6) tissues of endometriosis patients and non-endometriotic controls (CESCs, N = 6). hWJMSC-Exo were confirmed by flow cytometry, SEM, and DLS tests. Cells were treated with varying concentrations of ETN (0-40 μg/ml), hWJMSC-Exo (0-15 μg/ml), and their combination (E+E). IC50 values were determined using the MTT assay at 24, 48, and 72 hours. Protein levels of TNF- α, VEGF-A, and IL-10, and gene expression of MMP-2, MMP-9, MCP-1, aromatase, TSLP, and TGF-β1 were measured using ELISA and RT-PCR, respectively. RESULTS: The combination of ETN (10 μg/ml) and hWJMSC-Exo (10 μg/ml) at 24 and 48 hours, respectively, reduced protein expression of TNF-α, VEGF-A, and IL-10 in EESCs, EuESCs, and CESCs compared with untreated groups (P < 0.001). Additionally, E+E treatment significantly reduced mRNA expression of MMP-2, MMP-9, MCP-1, aromatase, TSLP, and TGF-β1 in all three groups compared to untreated groups. DISCUSSION: This combination therapy improves inflammation, angiogenesis, tissue remodeling, and immune regulation in endometriosis. However, clinical validation and long-term safety require further in vivo studies with larger sample sizes. CONCLUSION: E+E treatment synergistically reduced key cytokines and enzymes in endometriosis. This approach is a promising means of regulating inflammation.
Dysregulation of Key Biological Processes in Endometriosis Pathophysiology.
Mahdavi R, Akbari Jonoush Z, Mohammadi N … +7 more , Mousavi Salehi A, Ghadiri N, Sayadi M, Behravan M, Moramezi F, Ghafourian M, Farzaneh M
Curr Mol Med · 2025 Sep · PMID 40976896 · Publisher ↗
Endometriosis is a typical disorder affecting the female reproductive system and is characterized by the presence of tissue resembling the endometrium both within and beyond the pelvic cavity. Unfortunately, the etiology...
Endometriosis is a typical disorder affecting the female reproductive system and is characterized by the presence of tissue resembling the endometrium both within and beyond the pelvic cavity. Unfortunately, the etiology of endometriosis is not well understood. The purpose of this document is to create a summary of the factors contributing to endometriosis, especially the dysregulation of cellular and molecular pathways. Key biological processes implicated include enzyme dysregulation, exosome dysfunction, hormonal imbalances, apoptosis, angiogenesis, oxidative stress, epigenetic dysregulation, and the involvement of cytokines and chemokines. Many of these factors have overlapping pathways that can enhance the survival of endometrial debris and facilitate the implantation of endometrial tissue in extrauterine sites. This knowledge can provide a broader perspective on the onset and progression of endometriosis. Additionally, this study paves the way for the discovery of new therapeutic targets to improve the efficacy of endometriosis treatments and reduce the side effects associated with current treatments. Further research is needed to better understand the underlying mechanisms that lead to the dysregulation of diseaserelated pathways, which could ultimately be useful in early diagnosis and disease staging.
The Association Between Telomere Length and Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.
Khodabandelu S, Jahankhah S, Shabestari NM … +7 more , Eghbal Y, Khaleghi S, Hajizadeh A, Ghaheri SZ, Jafari M, Vosough M, Rahmanian M
Curr Mol Med · 2026 · PMID 40947687 · Publisher ↗
INTRODUCTION: Studies have stated that there has been a close association between the telomere length (TL) and the incidence of non-alcoholic fatty liver disease (NAFLD). The goal of this report is to explore the possibl...
INTRODUCTION: Studies have stated that there has been a close association between the telomere length (TL) and the incidence of non-alcoholic fatty liver disease (NAFLD). The goal of this report is to explore the possible association between TL and NAFLD. METHODS: This study adhered to the PRISMA guidelines for systematic reviews. An extensive literature search was conducted in the Cochrane Library, CINAHL, Scopus, PubMed, and Web of Science. The "meta" package in the R programming language, version 4.3.1, was used for statistical analysis. RESULTS: The meta-analysis of the included studies showed a pooled standard mean difference (SMD) of -0.25 (95% CI: -0.39 to -0.10), indicating shorter TL in NAFLD patients. Subgroup analyses revealed significant TL shortening in NAFLD patients with body mass index (BMI) <28 (SMD = -0.68, 95% CI: -0.96 to -0.39) and in case-control (-0.35, 95% CI: -0.51 to -0.20) and cohort studies (-0.68, 95% CI: -1.19 to -0.17). An odds ratio (OR) meta-analysis of six studies found that individuals with short TL had 1.72 times higher odds of NAFLD, which was statistically significant (95% CI: 1.23- 2.42, I = 85%). Excluding one study reduced heterogeneity (I = 37%) and increased the OR to 1.93 (95% CI: 1.45-2.56), confirming a strong association between short TL and NAFLD risk. DISCUSSION: The findings suggest a potential link between shorter TL and NAFLD. The odds ratio analyses further emphasized the increased risk of NAFLD in individuals with short TL. Nevertheless, the residual heterogeneity highlights the need for further high-quality, standardized research. CONCLUSION: Our findings supported the connection between reduced TL and NAFLD. Regardless of significant between-study diversity, the results remained consistent even after repeated sensitivity evaluations. Despite these findings, the high heterogeneity highlights the need for further well-designed studies to confirm TL as a reliable biomarker for NAFLD risk and progression.
The Role of Gut Microbiota in Modulating Inflammation and Insulin Resistance in Type 2 Diabetes Mellitus: Implications for Complication Management.
Kaabi YA
Curr Mol Med · 2025 Aug · PMID 40910235 · Publisher ↗
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and severe complications, including cardiovascular diseases, neuropathy, retinopathy, and nephropathy. This article exam...
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and severe complications, including cardiovascular diseases, neuropathy, retinopathy, and nephropathy. This article examines the role of gut microbiota in modulating inflammation and insulin resistance in type 2 diabetes mellitus (T2DM), as well as its implications for managing complications associated with the disease. We analyzed published literature to elucidate mechanisms linking microbial dysbiosis, impaired gut barrier function, and chronic inflammation to glycemic control and T2DM complications. Key findings suggest that gut microbiota dysbiosis contributes to systemic inflammation and insulin resistance, thereby exacerbating the complications of type 2 diabetes mellitus (T2DM). Therapeutic strategies, such as probiotics, prebiotics, and fecal microbiota transplantation, promise to improve glycemic control and mitigate complications by restoring microbial balance. This review provides a comprehensive framework for understanding the role of the gut microbiota in type 2 diabetes mellitus (T2DM) and highlights potential therapeutic interventions to enhance the management of complications.
Anti-Glioblastoma Effects of Dorzolamide Alone and in Combination with Temozolomide on U87 Cells and CD133+Glioblastoma Stem Cells.
Raza I, Naz K, Mubeen S … +6 more , Khan L, Naeem N, Wasim B, Shaikh S, Ghanchi NK, Hanif F
Curr Mol Med · 2025 Aug · PMID 40910234 · Publisher ↗
INTRODUCTION: Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a poor prognosis, primarily due to therapy resistance mediated by CD133+ glioblastoma stem cells (GSCs). The BCL3 gene contributes to th...
INTRODUCTION: Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a poor prognosis, primarily due to therapy resistance mediated by CD133+ glioblastoma stem cells (GSCs). The BCL3 gene contributes to this resistance and is potentially regulated by Carbonic Anhydrase II (CA II). Additionally, BCL3 enhances β-catenin-mediated transcription, promoting tumor growth. Since CA II may modulate both BCL3 expression and Wnt/β-catenin signaling, its inhibition represents a promising therapeutic strategy. Therefore, this study investigated the antiglioblastoma potential of the CA II inhibitor Dorzolamide, alone and in combination with Temozolomide (TMZ), in U87 cells and CD133+ GSCs. METHODS: U87 cells were treated with Dorzolamide, TMZ, or both. MTT, migration, invasion, TUNEL, and cell cycle assays assessed proliferation, motility, apoptosis, and cell cycle arrest. CD133+ GSCs were isolated by MACS and characterized by flow cytometry. Neurosphere assays and RT-qPCR analyzed neurosphere formation and mRNA expression of CA II, BCL3, β- catenin, and Twist, respectively. β-catenin protein expression was evaluated by immunocytochemistry. RESULTS: Dorzolamide and TMZ significantly inhibited proliferation, migration, and invasion while promoting apoptosis in U87 cells; the combination had the strongest effect (P<0.001). Cell cycle arrest occurred in G0/G1. Neurosphere formation by CD133+ GSCs was markedly reduced (P<0.001). Expression of CA II, BCL3, β-catenin, and Twist was significantly downregulated in all treatment groups (P<0.001). DISCUSSION: This study highlights FDA-approved CA II inhibitor Dorzolamide as a promising adjunct to TMZ therapy, effectively targeting GBM cells and therapy-resistant CD133+ GSCs. Its ability to inhibit CAII, BCL3, β-catenin, and Twist indicates its disruption of critical survival pathways in GSCs. However, further in vivo studies are required to confirm its therapeutic potential against GBM. CONCLUSION: Dorzolamide inhibits GSC proliferation, promotes apoptosis in U87 cells, affects the cell cycle, and enhances TMZ activity, suggesting potential in GBM treatment.
A Comprehensive Bibliometric Investigation on Antimicrobials from Fungal Origins with a Biotechnological Perspective.
da Silva Lopes L, Gontijo TS, Gonçalves AAM … +6 more , Silva Belo V, Prado Martin JG, Alves Silva K, Correa TDS, Campos-da-Paz M, Galdino AS
Curr Mol Med · 2025 Aug · PMID 40873275 · Publisher ↗
Interest in fungal research has increased in recent years due to its relevance in producing bioactive compounds, which serve as promising sources of bacteriostatic and fungistatic agents. Their use represents a significa...
Interest in fungal research has increased in recent years due to its relevance in producing bioactive compounds, which serve as promising sources of bacteriostatic and fungistatic agents. Their use represents a significant alternative to traditional antibiotics, minimizing the risks associated with microbial resistance. In this context, the present work aimed to: assess the volume of annual publications on the subject and identify key players, analyze the collaboration network among researchers, and check the patents filed on this topic For this purpose, the Bibliometrix R-package, as well as scientific metadata from the Web of Science and Scopus databases, were used (n=506). In total, 256 sources, authors (n=2,526), keywords (n=1,812), and references (n=19,315), from 1989 to 2023, were analyzed. The academic debate on the subject has been promoted by India (29%), the United Kingdom (UK) (7%), China (6%), and the United States of America (USA) (6%). The authors identified as the most cited were Liu J (n = 142), followed by Jesu Arockiaraj (n = 106). A knowledge predominance of publications focusing on the life science disciplines. The most prolific institutions were the National Research Center (n=20) and the University of Pittsburgh (n=13). The most cited journals were the World Journal of Microbiology & Biotechnology (n=719) and Applied Microbiology and Biotechnology (n=661). Finally, the United States Patent and Trademark Office represented 85% of the patents filed on the subject (n=28,303). Collectively, the findings herein can guide researchers and biotechnology industries in identifying the most relevant sources for antimicrobial biotechnology.
Transcriptome Analysis, Machine Learning, and Experimental Identification of CDK7 Affecting the Progression of Pregnancyinduced Hypertension by Influencing Macrophage Polarization.
Gu S, Zhou X, Shen X … +3 more , Xiao C, Gao C, Zhang X
Curr Mol Med · 2025 Aug · PMID 40873178 · Publisher ↗
INTRODUCTION: Pregnancy-induced hypertension (PIH) is a severe pregnancy complication characterized by placental insufficiency, abnormal vascular remodeling, and immune dysregulation, but personalized therapeutic markers...
INTRODUCTION: Pregnancy-induced hypertension (PIH) is a severe pregnancy complication characterized by placental insufficiency, abnormal vascular remodeling, and immune dysregulation, but personalized therapeutic markers remain unclear. This study aimed to identify key genes and explore immune mechanisms in PIH using transcriptome analysis, machine learning, and experimental validation. METHODS: We analyzed the GSE204835 transcriptomic dataset to screen differentially expressed genes (DEGs) and performed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, and Gene Set Enrichment Analysis (GSEA) for functional annotation. Immune infiltration analysis was also performed to examine the immune landscape in PIH. Least Absolute Shrinkage and Selection Operator (LASSO) regression identified key genes, which were validated in a PIH cell model. Flow cytometry and immunofluorescence assays assessed the effect of CDK7 knockdown on macrophage polarization. RESULTS: A total of 1,598 DEGs (1,123 upregulated, 475 downregulated) were identified. Enrichment analyses highlighted associations with embryonic organ development, oxidative phosphorylation, angiogenesis, and oxidative stress. Immune infiltration analysis revealed altered eosinophil and macrophage polarization in PIH. LASSO regression selected 12 key genes, with CDK7 showing the most significant upregulation in the PIH model. CDK7 knockdown promoted macrophage polarization toward the anti-inflammatory M2 phenotype. DISCUSSION: These findings link CDK7 to immune dysregulation in PIH by modulating macrophage polarization, expanding our understanding of PIH's molecular mechanisms. The study's limitations include reliance on public datasets and in vitro models, warranting in vivo validation. CONCLUSION: CDK7 emerges as a potential therapeutic target for PIH, offering new insights into immunoregulatory interventions for this complication.
Integrating Traditional Medicine with Conventional Therapies to Combat Tuberculosis: A Comprehensive Review.
Gaurav A, Fatima Z, Yaqinuddin A … +1 more , Hameed S
Curr Mol Med · 2025 Aug · PMID 40849745 · Publisher ↗
Tuberculosis (TB) poses a serious public health risk and is a hot topic in the international health forums. Global health organizations emphasize the importance of effectively managing and eradicating TB. The emergence o...
Tuberculosis (TB) poses a serious public health risk and is a hot topic in the international health forums. Global health organizations emphasize the importance of effectively managing and eradicating TB. The emergence of drug-resistant TB and the elevated risk of hepatotoxicity associated with anti-TB medications have highlighted the need for reevaluation of existing TB drugs. These challenges have led to prolonged dosing schedules and increased dosages to combat resistance and effectively eliminate the disease. In India, the government revised the National Tuberculosis Control Program to address this growing concern. India is home to six well-established traditional medical systems: Ayurveda, Siddha, Unani, Yoga, Naturopathy, and Homoeopathy (collectively known as AYUSH). This review compares the effectiveness of traditional medicinal regimens with conventional TB treatment. Herbal extracts used in Ayurveda, Siddha, and Unani offer promising alternatives for TB treatment, potentially reducing hepatotoxicity and liver damage while combating antibiotic resistance. These natural remedies are generally safe for consumption in larger quantities, cost-effective to produce, and free from harmful toxins. The findings in this article provide scientific support for the anti-TB potential of the diverse medical systems recognized by India's Ministry of AYUSH.
Genistein - A Broad-spectrum Bioactive Compound with Diverse Pharmacological Potential: A Systematic Review.
Goswami M, Kityania S, Nath R … +5 more , Nath P, Nath D, Das S, Sharma BK, Talukdar AD
Curr Mol Med · 2025 Jul · PMID 40734425 · Publisher ↗
INTRODUCTION: Genistein is an isoflavone primarily extracted from soybeans and the Dyer's broom (Genista tinctora L.). It has been extensively studied using various extraction methods and characterized via NMR for struct...
INTRODUCTION: Genistein is an isoflavone primarily extracted from soybeans and the Dyer's broom (Genista tinctora L.). It has been extensively studied using various extraction methods and characterized via NMR for structural elucidation. Its pharmacological potential, mediated through interactions with multiple receptors and signalling pathways, has been validated through numerous preclinical studies globally. METHODS: To analyze the pharmaceutical profile of genistein using PASS software, we correlated it with existing literature, and evaluated its efficacy against various diseases. The study aims to explore the broad-spectrum potential of genistein as a lead compound against the various diseases such as cancer, cardiovascular disease (CVD), neurodegenerative and viral diseases. RESULTS: It is a broad-spectrum drug that is effective against - cancer, heart associated diseases, neurodegenerative diseases and viral diseases. It is a potential anticancer drug that modulates apoptosis, cell cycle, metastasis, and regulates the cancer signalling pathways. Based on the compilation of reports from the literature reviews, it is effective against breast cancer (23%), neuroblastoma (12.77%), prostate and lung cancer (10.64%). Secondly, it has cardio protectant properties and supports cardiovascular health by improving endothelial function and lowering cholesterol. It is reported to be effective against cardiac dysfunction (38.46%), atherosclerosis (26.92%), and cardiotoxicity (15.39%). Thirdly, it offers various neuroprotective benefits in neurodegenerative diseases like Alzheimer's (69.84%) and Parkinson's (19.05%). Lastly, it was also reported to be effective against HSV (23.08%), HIV (23.08%) and HPV (15.39%) viral infections. DISCUSSION: Genistein exhibits a wide range of therapeutic properties, including anticancer, cardioprotective, neuroprotective, and antiviral effects. It has shown notable efficacy in treating cancers such as breast, prostate, and lung, as well as neurodegenerative conditions like Alzheimer's and Parkinson's. Additionally, its benefits in improving cardiovascular health and combating viral infections further support its potential as a multifunctional therapeutic agent. Although genistein has a broad pharmacological spectrum, its clinical relevance is hampered by a suboptimal pharmacokinetic profile, such as poor bioavailability, rapid systemic clearance, extensive first-pass metabolism, and low aqueous solubility, which limit its therapeutic efficacy. CONCLUSIONS: This systematic review highlights genistein's pharmacological profile, demonstrating its efficacy against various diseases and its potential as a lead candidate for drug development in oncology, cardiovascular health, and neurodegenerative therapies. Thus, underscoring its potential, Genistein can be considered a versatile therapeutic agent.
A Cross-sectional Data Analysis between Serum Total Bilirubin and Potential Obesity Indices in US Adults.
Tian L, Zhang JG, Chen Y … +3 more , Feng Y, Liu Q, Ling C
Curr Mol Med · 2025 Jul · PMID 40708510 · Publisher ↗
INTRODUCTION: Obesity is a major risk factor for metabolic and cardiovascular disorders. Recently, emerging biomarkers, such as the Visceral Adiposity Index (VAI) and Lipid Accumulation Product (LAP), have garnered atten...
INTRODUCTION: Obesity is a major risk factor for metabolic and cardiovascular disorders. Recently, emerging biomarkers, such as the Visceral Adiposity Index (VAI) and Lipid Accumulation Product (LAP), have garnered attention for their utility in assessing visceral obesity. Bilirubin, a potent endogenous antioxidant, has been associated with protective effects against various diseases. This study aims to investigate the relationship between serum total bilirubin (STB) levels and VAI/LAP in adults. METHODS: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) collected between 2003 and 2020. The calculation of VAI and LAP was performed computationally. Weighted multivariate regression models were used to explore the potential correlation between STB levels and VAI or LAP. RCS curves were used to identify the potential non-linear relationship. Moreover, subgroup analyses were conducted to examine heterogeneity across different populations. RESULTS: The analysis included a cohort of 10,625 individuals aged 20 to 85 years. Both unadjusted and adjusted statistical models revealed a significant negative association between STB levels and VAI or LAP (all P< 0.001). RCS indicates that these relationships are linear. Subgroup analyses identified particularly strong associations in non-smokers aged 20-59 without hypertension/diabetes (P < 0.05). DISCUSSION: Our study's strengths include the use of nationally representative data with appropriate weighting, comprehensive adjustment for confounding variables, and pioneering research on the link between serum bilirubin levels and visceral fat indices, which may indicate early metabolic risk markers. This finding highlights the significant role of bilirubin in body fat distribution and lipid metabolism. CONCLUSION: This study revealed that STB was associated with VAI or LAP among the specific general American population aged 20-59 without hypertension/diabetes. Further prospective investigations are warranted to clarify the temporal relationship between STB and novel obesity indices.
Functional Analysis of miR-148a: A Differentially Expressed microRNA in Hemifacial Microsomia.
Huang N, Sun M, Zhang Y … +1 more , Zhang Q
Curr Mol Med · 2025 Jul · PMID 40708509 · Publisher ↗
INTRODUCTION: Hemifacial Microsomia (HFM) is the second most common congenital deformity, yet its etiology and pathogenesis remain unclear. Therefore, this study aimed to identify differentially expressed microRNAs (miRN...
INTRODUCTION: Hemifacial Microsomia (HFM) is the second most common congenital deformity, yet its etiology and pathogenesis remain unclear. Therefore, this study aimed to identify differentially expressed microRNAs (miRNAs) between healthy and affected bone marrow mesenchymal stem cells (BMSCs) from HFM patients, focusing on the functional roles of miR-148a in osteogenesis and osteoclastogenesis. METHODS: The specific expression of microRNAs was screened by sequencing and verified by PCR. Through the use of mimics, inhibitors, and knockout technology, we controlled the expression of miR-148a in vivo and in vitro. Osteogenesis and osteoclastogenesis induction, PCR, western blot, ALP staining, alizarin red staining, TRAP staining, micro-CT, and tissue sections were performed to explore the effects of miR-148 on osteogenesis and osteoclastogenesis. RESULTS: MiR-148a was identified and confirmed through our research as a differentially expressed miRNA in HFM. Overexpression of miR-148a increased osteogenesis-related gene and protein expression and mineralized calcium nodule formation while decreasing osteoclast-related gene and protein levels. Silencing or knockout of miR-148a produced opposite effects. miR-148a knockout mice were smaller than wild-type, with reduced osteogenesis, fewer trabeculae, increased trabecular bone separation in the mandible, and decreased ramus length. Additionally, local overexpression of miR-148a in knockout mice increased local bone mass. DISCUSSIONS: The current study findings demonstrate that miR-148a can influence the bone volume, and its role in chondrogenesis deserves further research. Additionally, further studies on the changes upstream of miR-148a that lead to differences in miR-148a expression between the healthy and affected sides of HFM patients and the differences in bone size are warranted to better understand HFM pathogenesis. CONCLUSION: Our findings suggest that the opposing effects of miR-148a on osteogenesis and osteoclastogenesis lead to decreased bone mass in HFM. Local overexpression can reverse bone defects caused by miR-148a, suggesting its promising role in future treatments. We anticipate that further investigations will enhance our understanding and ultimately pave the way for the application of these insights in clinical settings for disease treatment.
Genetic Association Between Sleep Traits and Vertigo Risk: A Two-Sample Bidirectional Mendelian Randomization Study.
Xu W, Tian E, Wang J … +4 more , Yu X, Guo Z, Chen J, Zhang S
Curr Mol Med · 2025 Jul · PMID 40653840 · Publisher ↗
<p>Background: Observational studies suggest the potential association between sleep traits and vertigo; however, causal evidence remains limited. </p><p> Objective: This study aimed to explore the relationship between g...
<p>Background: Observational studies suggest the potential association between sleep traits and vertigo; however, causal evidence remains limited. </p><p> Objective: This study aimed to explore the relationship between genetically predicted sleep traits and vertigo with the Mendelian randomization (MR) method.</p><p> Methods: Instrumental variables for sleep traits (snoring, sleep duration, insomnia, daytime sleepiness, daytime napping, and chronotype) were adopted from genomewide association studies (GWAS) data of European ancestry from UK Biobank. The summary-level datasets of vertigo were retrieved from the GWAS of FinnGen. Inversevariance weighted (IVW) method was adopted as the main analysis.</p><p> Results: IVW analysis revealed a significant association between genetically predicted daytime napping (OR = 1.51, 95% CI =1.08-2.12, P = 0.016) and chronotype (OR = 1.13, 95% CI =1.01-1.26, P = 0.033), both of which were associated with an increased risk of vertigo. However, we did not find evidence for a causal effect of snoring, overall sleep duration, long sleep duration, short sleep duration, insomnia, and excessive daytime sleepiness on vertigo. No reverse causality was detected.</p><p> Conclusion: Our findings suggest that abnormal sleep patterns may serve as risk factors for vertigo disorders and offer opportunities for the prevention and management of vertigo disorders.</p>.
M1 Macrophage-derived TNF-α Promotes Pancreatic Cancer Ferroptosis via p38 MAPK-ACSL4 Pathway.
Zhang JC, Yin HL, Chen QD … +4 more , Zhao GC, Pu N, Lou WH, Wu WC
Curr Mol Med · 2026 · PMID 40653839 · Publisher ↗
INTRODUCTION: Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most malignant gastrointestinal tumors. M1 macrophage, a subtype within the Tumor Microenvironment (TME), plays a vital role in the development of cance...
INTRODUCTION: Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most malignant gastrointestinal tumors. M1 macrophage, a subtype within the Tumor Microenvironment (TME), plays a vital role in the development of cancer. Despite its anti-tumoral functions, the specific mechanisms of its action remain incompletely understood. METHODS: The effect of M1 macrophages on the proliferation ability and cell viability of PDAC cells was evaluated by Cell Counting Kit-8 (CCK-8) cell proliferation assay, cell clone formation assay, and flow cytometry. Western blot, qRT-PCR, confocal microscope, RNA-sequencing, and transmission electron microscope were performed to assess lipid peroxidation and ferroptosis level of PDAC cells in the context of M1 macrophage or TNF-α. RESULTS: M1 macrophages inhibited cell proliferation and promoted cell death of PDAC cells, in which ferroptosis played a vital role. Mechanistically, Tumor Necrosis Factor-alpha (TNF-α) released by M1 macrophages binds to the TNFR1 receptor on pancreatic cancer cells, activating the p38 MAPK signaling, which upregulates Acyl-CoA Synthetase Long-chain family member 4 (ACSL4) expression, a critical lipid metabolism enzyme linked to ferroptosis, thereby promoting ferroptosis. Knockdown of ACSL4 or TNFR1 significantly reduced TNF-α-induced ferroptosis. DISCUSSION: TNF-α is a major inflammatory cytokine and is mainly generated by macrophages and T lymphocytes. It is involved in many pathological processes, such as inflammatory diseases, autoimmune diseases, and cancer. Studies have shown that the administration of recombinant TNF-α can induce tumor regression in mice with sarcomas. In our study, systemic injection of TNF-α slowed the tumor growth in nude mice, but with no significant difference compared with the control group, which may partially be attributed to its angiogenic activity. TNF-α signals via two distinct membrane-binding receptors, TNFR1 and TNFR2, which regulate various diseases. In pancreatic cancer, the role of TNF-α is complex and poorly understood. In a previous study, they found that exogenous systemic administration of human TNF-α, which interacted with murine TNFR1, significantly increased overall tumor growth in the Panc02-PDAC model. Intriguingly, the loss of TNFR1 led to an impediment of immune cell infiltration into the tumor and impaired immunosurveillance, which accelerated tumor growth. This suggests that TNFR1 exerts both protumoral and anti-tumoral functions in the Panc02-PDAC model, but the overall outcome is likely dependent on the spatiotemporal availability of TNF-α. However, systemic TNF-α injection can lead to severe side effects in animals, limiting its further application. In a recent study, TNFR2 was found to promote tumorigenesis and progression in the KPC-PDAC model. Knockdown of TNFR2 or pretreatment with an anti-TNFR2 antibody could significantly slow the tumor progression and incidence. In our study, TNFR2 was found to have a low expression in pancreatic cancer cells and was barely detected with the failure of knockdown. However, the cell lines used in the former study were established from a KPC mouse model, while our experiments were conducted using human PDAC cell lines. Contrary findings are possible as cell lines originate from two different species. However, we will further investigate the mechanism of this difference. CONCLUSION: In summary, this study revealed that M1 macrophages could induce ferroptosis in pancreatic cancer cells through secreting TNF-α, indicating a potential therapeutic option for PDAC.
Plasma Sphingomyelin Levels Mediate the Causal Relationship Between Gut Microbiota and Myocardial Interstitial Fibrosis: A Mendelian Randomization Study.
Yu M, Huang X, Gao B … +1 more , Huang J
Curr Mol Med · 2025 · PMID 40653838 · Publisher ↗
BACKGROUND: Prior studies established associations between gut microbiota and myocardial interstitial fibrosis. Nevertheless, the causal relationships and potential intermediaries remain unknown. Thus, we employed a Mend...
BACKGROUND: Prior studies established associations between gut microbiota and myocardial interstitial fibrosis. Nevertheless, the causal relationships and potential intermediaries remain unknown. Thus, we employed a Mendelian randomization strategy to explore whether gut microbiota causally influence myocardial interstitial fibrosis and to assess whether plasma metabolites serve as potential intermediaries in this pathway. METHODS: A two-sample Mendelian randomization approach was performed, utilizing genome-wide association studies to examine the causal relationship between gut microbiota (n= 18,340) and myocardial interstitial fibrosis (n=41,505). Additionally, an investigation was conducted to determine the potential mediation by four plasma metabolites (n=8,299) via a two-step Mendelian randomization analysis. Inverse variance weighted method was the primary method employed in Mendelian randomization, and complementary analyses were conducted alongside to enhance the robustness of the results. RESULTS: Mendelian randomization analysis indicated suggestive associations of three microbial taxa with myocardial interstitial fibrosis. The most significant taxon was the genus Faecalibacterium (β [SE], -0.1272 [0.0347], P = 0.0002). Reverse Mendelian randomization analyses revealed no evidence of myocardial interstitial fibrosis affecting these three microbial taxa. In the two-step Mendelian randomization analysis involving four plasma metabolites, it was found that plasma sphingomyelin levels mediated the causal effects of genus Faecalibacterium on myocardial interstitial fibrosis (proportion mediated = 14.2%, 95% CI = 1.4-27.0%). CONCLUSION: The study validates the causality between particular gut microbial taxa and myocardial interstitial fibrosis, and suggests that plasma sphingomyelin might mediate this association. These findings offer a novel perspective on myocardial interstitial fibrosis prevention, and underscore the significance of plasma sphingomyelin in human health and disease.
A Comparative Review of Methods for Detecting Epidermal Growth Factor Receptor Mutations in Cell-Free DNA from Lung Cancer Patients.
Shohani S, Barati M, Hosseini A
Curr Mol Med · 2025 Jul · PMID 40635223 · Publisher ↗
BACKGROUND: Lung cancer remains the leading cause of cancer-related mortality. Determining the T790M resistance variants and epidermal growth factor receptor (EGFR) mutations is crucial for personalized treatment, especi...
BACKGROUND: Lung cancer remains the leading cause of cancer-related mortality. Determining the T790M resistance variants and epidermal growth factor receptor (EGFR) mutations is crucial for personalized treatment, especially when using targeted therapies. OBJECTIVE: This review article aims to comprehensively compare some of the various diagnostic techniques associated with liquid biopsies, such as cell-free DNA (cfDNA) for T790M and EGFR mutant identification. It also aims to evaluate their pertinence in clinical settings, as well as their sensitivity and specificity to determine how effectively they monitor treatment response and resistance. METHODS: A literature search was conducted using databases including PubMed, Scopus, and Web of Science. The keyword list included "EGFR mutations," "T790M resistance," "liquid biopsy," "COLD PCR," "NGS," "ddPCR," "BEAMing," and other methods. The effect of these studies on diagnostic technologies for identifying EGFR mutations was assessed in terms of clinical practice, methodological accuracy, and significance. Sensitivity, specificity, clinical applicability, cost analysis, turnaround times, and ease of integration into clinical workflows were used as parameters for evaluation based on the literature. RESULTS: There are advantages and disadvantages to cfDNA monitoring strategies for treatment response and resistance, as well as to the assessment of sensitivity, specificity, and clinical applicability for identifying EGFR mutations. CONCLUSION: Advanced techniques such as COLD-PCR, LC-MS, qPCR, NGS sequencing, Sanger sequencing, PNA microarrays, the Allele-Specific Competitive Extension (ASCE) real-time PCR assay, and nanopore technology are necessary for personalized lung cancer management. However, depending on the objective of the work, the suitable method should be selected based on its benefits and drawbacks.
Expression and Function of Vasopressin Receptors in the HT-29 Cell Line.
Tuncdemır BE, Ozer ES
Curr Mol Med · 2025 Jul · PMID 40635222 · Publisher ↗
INTRODUCTION: Vasopressin receptors can have different effects on tumorigenesis. The in vitro usage of agonists and antagonists of these receptors can also have a potential impact on developing adjuvant treatment options...
INTRODUCTION: Vasopressin receptors can have different effects on tumorigenesis. The in vitro usage of agonists and antagonists of these receptors can also have a potential impact on developing adjuvant treatment options. Therefore, we aimed to demonstrate the expression and function of vasopressin receptors in the HT- 29 cell line, which is one of the cell lines frequently used in colorectal cancer studies. Colorectal cancer is one of the most prevalent cancer types worldwide. There are many risk factors for colorectal cancer, including unhealthy lifestyle and social environment, and early diagnosis can enhance the survival of patients. Main treatment strategies aim to slow down the progression of cancer, increase survival, and enhance the quality of life. Investigating the relationship between colorectal cancer and vasopressin receptors has been an interesting research area in terms of developing new treatment strategies lately. METHODS: For receptor expression and functional analysis, RT-PCR experiments and cAMP accumulation assay were performed. RESULTS: The expression of V2R and V1aR was observed in HT-29 cells, and V2Rs demonstrated their function as cAMP responders after treatment with agonists and antagonists. DISCUSSION: This is the first study to report that V2R and V1aR expressions were detected by RT-PCR, and the functionality of V2R was analyzed by cAMP accumulation assay after treating HT-29 cells with agonists and antagonists. CONCLUSION: We hope that these results may contribute to colorectal cancer research and the development of novel therapeutic strategies targeting vasopressin receptor signaling pathways.
Loss of ARHGAP40 in Breast Cancer by Hypermethylation and its Clinical Significance.
Tao Y, Wang J, Ren X … +3 more , Gu L, Sun J, Wang J
Curr Mol Med · 2026 · PMID 40635221 · Publisher ↗
OBJECTIVE: ARHGAP40 is a Rho GTPase-activating protein (RhoGAP). The expression and biological roles of ARHGAP40 in breast cancer are unknown. We aimed to investigate the expression of ARHGAP40 and its epigenetic mechani...
OBJECTIVE: ARHGAP40 is a Rho GTPase-activating protein (RhoGAP). The expression and biological roles of ARHGAP40 in breast cancer are unknown. We aimed to investigate the expression of ARHGAP40 and its epigenetic mechanism in breast cancer. METHODS: The expression level of ARHGAP40 was examined in breast cancer cell lines and tissues. The methylation status of ARHGAP40 was analyzed using a bisulfite sequencing PCR (BSP). The biological roles of ARHGAP40 in breast cancer were investigated. RESULTS: ARHGAP40 mRNA was significantly expressed in MCF-7 and weakly in MDA-MB-231, whereas methylated ARHGAP40 was detected in MDA-MB-231 and partly in MCF-7. ARHGAP40 protein was positively expressed in normal breast epithelial cells in all paracancerous tissues. The expression level of ARHGAP40 was significantly associated with age, TNM stage, lymph node metastasis, molecular subtypes, proliferative marker Ki67, and HER2 expression. The overall survival (OS) of patients with high expression of ARHGAP40 was longer than those with low expression. Overexpression of ARHGAP40 in MCF-7 and MDA-MB-231 cells induced apoptosis and suppressed cell proliferation. The opposite outcomes were observed in the ARHGAP40 knockdown experiment. CONCLUSION: Our data suggested ARHGAP40 to be downregulated in breast cancer due to hypermethylation. ARHGAP40 was found to act as a tumor suppressor in breast cancer and could be a potential therapeutic target for breast cancer.
The Mechanosensitive Ion Channel Piezo1 Promotes Obliterative Bronchiolitis through YAP-Dependent Epithelial-to-Mesenchymal Transition.
Wan L, Wu Y, Yang J … +3 more , Deng P, Yao Z, Sun Q
Curr Mol Med · 2025 Jul · PMID 40626526 · Publisher ↗
INTRODUCTION: Obliterative bronchiolitis (OB) is a severe and progressive complication characterized by the fibrotic obliteration of small airways, leading to significant morbidity and mortality, particularly in lung tra...
INTRODUCTION: Obliterative bronchiolitis (OB) is a severe and progressive complication characterized by the fibrotic obliteration of small airways, leading to significant morbidity and mortality, particularly in lung transplant recipients. The pathogenesis of OB involves complex cellular processes, among which epithelial-tomesenchymal transition (EMT) plays a crucial role. This study investigates the role of mechanosensitive ion channel Piezo1 in promoting OB through Yes-associated protein (YAP)-dependent EMT. METHOD: Piezo1-induced signal pathway alterations, fibrosis, and EMT-related features were examined in the mouse OB model and BEAS-2B cells. The efficacy of Piezo1 in EMT and OB was explored and validated both in vitro and in vivo. RESULTS: Piezo1 was found to be upregulated in OB, and pharmacological inhibition of Piezo1 effectively alleviated EMT and fibrotic deposition. Piezo1 activation stimulated the Ca2+ influx and nuclear translocation of YAP that triggered the transition of epithelial cells into a mesenchymal phenotype, which contributed to airway fibrosis and obstruction. Furthermore, inhibition of YAP or calcium chelation significantly attenuated Piezo1 activation-induced EMT and OB, indicating that YAP and Ca2+ are critical mediators in this process. DISCUSSION: Piezo1 expression was found to be upregulated in OB, and its activation induced the epithelial-to-mesenchymal transition (EMT) process via a YAP-dependent pathway. Piezo1 could accelerate EMT and the occlusion rate of grafts via Ca2+ influx-dependent YAP activation in OB, suggesting a direct role in facilitating EMT and subsequent fibrotic remodeling in OB. CONCLUSION: The present results highlight that Piezo1 promotes OB through a YAPdependent EMT pathway, suggesting Piezo1 as a novel therapeutic strategy for treating OB and potentially improving outcomes of lung transplant recipients.
SLC41A2 Suppresses Colon Cancer Progression by Inhibiting GSK3β Ubiquitin-proteasome Degradation.
Lu Y, Shen Y, Liu J … +4 more , Deng J, Wang Y, Liu Q, Lu W
Curr Mol Med · 2025 Jul · PMID 40626525 · Publisher ↗
BACKGROUND: Colon cancer is a highly prevalent tumor with a high mortality rate worldwide. SLC41A2 is a member of the solute carrier family, but its role in colon cancer is still unclear. METHODS: The relationship betwee...
BACKGROUND: Colon cancer is a highly prevalent tumor with a high mortality rate worldwide. SLC41A2 is a member of the solute carrier family, but its role in colon cancer is still unclear. METHODS: The relationship between the expression level of SLC41A2 and clinicopathological features in colon cancer was investigated using data from the TCGA database. The differential expression genes of SLC41A2 were identified the potential role of SLC41A2 in colon cancer was analysed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. By transfecting plasmids or siRNA to overexpress or knock down SLC41A2 in colon cancer cells, the effects of SLC41A2 on colon cancer cell proliferation, migration, and apoptosis were detected through EdU, MTT, wound-healing, Transwell, and JC-1 experiments. Western blot and ubiquitination experiments validated the regulation of GSK3β stability by SLC41A2. Rescue experiments and CCK8 assays confirmed the regulatory effect of SLC41A2 on GSK3β. RESULTS: Compared to normal tissues, SLC41A2 exhibited a lower expression level in colon cancer, and the expression levels of SLC41A2 were correlated with the stage and Tumor Node Metastasis (TNM) classification. GO and KEGG analyses displayed that SLC41A2 primarily affected the growth factor activity and Wnt signaling pathway. Furthermore, elevated expression of SLC41A2 notably decreased the proliferation, migration and invasion of colon cancer cells, along with increased apoptosis. The overexpression of SLC41A2 and rescue experiments confirmed that SLC41A2 enhances the protein stability of GSK3β by inhibiting its ubiquitin-proteasome degradation and causes the upregulation of GSK3β, thereby suppressing the progression of colon cancer. CONCLUSION: SLC41A2 was lowly expressed in colon cancer tissues or cells. By inhibiting the ubiquitin-proteasome degradation of GSK3β, SLC41A2 can significantly upregulate the expression of GSK3β, which ultimately suppresses the proliferation and migration of colon cancer cells.
Triple Negative Breast Cancer Heterogeneity and Tumour Microenvironment-based Model Systems' Focus on Druggable Targets.
Kundu S, Suresh PK
Curr Mol Med · 2025 · PMID 40621763 · Publisher ↗
Fifteen to twenty percent of all cases of breast cancer are TNBC (triple negative breast cancer) and exhibit heterogenic features due to their diverse molecular characteristics. Additionally, their aberrant cell cycling...
Fifteen to twenty percent of all cases of breast cancer are TNBC (triple negative breast cancer) and exhibit heterogenic features due to their diverse molecular characteristics. Additionally, their aberrant cell cycling behavior contributes to their metastatic capabilities and aggressive nature. TNBC is the only molecular subtype, which lacks the expression of hormone receptors, like estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2). Hence, it is recalcitrant to hormone therapy. Also, the complex and evolving tumour microenvironment (TME) comprises blood vessels, stromal cells, immune cells, metabolic factors, extracellular matrix (ECM), and an integrated perspective of their interconnections as well as their variability with respect to TNBC progression needs to be comprehended for biomarker/druggable target(s) development and/or their validation. Such TME-based model systems can help us understand the relationship between the different TME components that affect tumour growth and metastasis. This review also catalogs biomarkers and TNBC behaviour within the TME. Also, this review discusses and analyses models that replicate various tumour subtypes that can be correlated with variability in treatment responses, thereby facilitating a better understanding of TNBC heterogeneity. Thus, by identifying biomarkers and constructing model systems, we can augment efforts to overcome treatment failure and poor outcomes in TNBC patients. These subtype-specific TNBC model systems, mirroring the intricacies of the TME, have the potential to provide a feasible and innovative approach to target TNBC cells. This review will facilitate the ongoing global efforts to develop efficacious and safe "tailor-made" drugs for TNBC patients.
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