Current Molecular Medicine[JOURNAL]
Sun
200 papers
Network-based Transcriptomic Profiling of Fetal Astrocyte Differentiation Reveals Therapeutic Targets for Neurodegenerative Disease.
Moftakhar-Bazkiaei A, Farzaneh M
Curr Mol Med · 2026 Apr · PMID 41935371 · Publisher ↗
INTRODUCTION: Neurodegenerative disorders, including Alzheimer's Disease (AD), Parkinson's Disease (PD), and Age-related Macular Degeneration (AMD), are marked by the progressive loss of specific neuronal populations. As...
INTRODUCTION: Neurodegenerative disorders, including Alzheimer's Disease (AD), Parkinson's Disease (PD), and Age-related Macular Degeneration (AMD), are marked by the progressive loss of specific neuronal populations. Astrocytes, the glial cells surrounding neurons, play a critical role in maintaining neuronal health by providing neurotrophic support, producing antioxidants, and clearing waste. Dysfunctional astrocytes contribute to disease progression, yet their developmental trajectory and molecular regulation remain incompletely understood. METHOD: This study aims to computationally characterize transcriptional differences between fetal astrocytes and neural stem cell lines to identify key regulatory genes, pathways, and therapeutic targets relevant to astrocyte-linked neurodegeneration. Using microarray data and bioinformatics pipelines, 359 Differentially Expressed Genes (DEGs) were identified, including 249 upregulated and 110 downregulated transcripts. RESULTS: Protein-Protein Interaction (PPI) network analysis revealed ten hub genes- COL1A1, TIMP1, LOX, COL6A1, COL6A3, COL5A1, CD44, LTBP2, ACTA2, and PLAU-central to extracellular matrix remodeling and cell adhesion. Drug-gene interaction analysis linked these genes to compounds such as Estradiol valerate, Retinoic acid, and Calcitriol, suggesting therapeutic relevance. DISCUSSION: Enrichment analysis highlighted transcriptional regulation, apoptosis, and ECM-receptor interaction as dominant biological themes. Key miRNA-mRNA interactions, including hsa-miR-877-5p and hsa-miR-767-5p targeting LOX and COL6A3 were also identified. CONCLUSION: Overall, this study integrates transcriptomic profiling, network modeling, and drug-gene interaction analysis to uncover astrocyte-specific molecular targets, offering a computational framework for therapeutic exploration in neurodegenerative disease.
Gut Microbiota and Metabolic Profiles Reveal the Mechanism of Weight Loss in Patients with Obesity Stimulated By Acupuncture.
Huo Y, Gao J, Lv Y … +1 more , Ai B
Curr Mol Med · 2026 Mar · PMID 41930918 · Publisher ↗
INTRODUCTION: This study aims to elucidate the mechanisms underlying the efficacy of Quantitative Lifting And Inserting Acupuncture (QLIA) in treating simple obesity through integrated metabolomic and gut microbiota anal...
INTRODUCTION: This study aims to elucidate the mechanisms underlying the efficacy of Quantitative Lifting And Inserting Acupuncture (QLIA) in treating simple obesity through integrated metabolomic and gut microbiota analyses. METHODS: Thirty patients with obesity were randomized into treatment (QLIA), control (standard needle lifting), and healthy groups (standard needle lifting) (n=10 each). Acupuncture was administered three times per week for 8 weeks. 16S rRNA sequencing was performed on fecal samples, and serum samples were analyzed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLCMS/ MS) metabolomics. RESULTS AND DISCUSSION: QLIA significantly altered gut microbiota α-diversity and β- diversity. The Firmicutes/Bacteroidetes ratio was significantly increased in the QLIAtreated group. The treatment group showed increased abundance of beneficial bacteria such as Bifidobacterium and Dialister, and decreased abundance of potentially harmful bacteria such as Escherichia-Shigella. KEGG pathway analysis revealed upregulation of amino acid biosynthesis and carbohydrate metabolism pathways and downregulation of nucleotide biosynthesis pathways in the gut microbiota. Metabolomic analysis showed significantly elevated levels of acetyl-Lcarnitine and decreased levels of N-acetylneuraminic acid in the treatment group after acupuncture. PICRUSt analysis primarily implicated amino acid metabolic pathways. Serum metabolite analysis identified lipid, carbohydrate, and amino acid metabolism pathways as key targets of acupuncture intervention. Comparative analysis of metabolic pathways revealed amino acid metabolism as a shared target in both gut microbiota and serum metabolite profiles. These findings suggest that QLIA exerts its weight-loss effects by reshaping the gut microbiota structure and modulating host metabolic profiles, thereby highlighting a synergistic mechanism involving the gut-host metabolic axis. CONCLUSION: QLIA significantly promoted weight loss in simple obesity by modulating key metabolic pathways and altering gut microbiota composition. The study provides insight into the mechanisms underlying acupuncture-induced weight loss and supports its potential as a therapeutic option for obesity.
Overexpression of Membrane Metalloendopeptidase Attenuates Oxidative Stress and Inflammation in Diabetic Neuropathy via the Nrf2/HO-1 Pathway.
Liu Z, Ge J, Sun J … +4 more , Yang X, Su Q, Sun X, Du B
Curr Mol Med · 2026 Mar · PMID 41930917 · Publisher ↗
OBJECTIVE: To investigate the role of Membrane Metalloendopeptidase (MME) in oxidative stress and inflammation in painful diabetic neuropathy, and to explore the underlying mechanism. METHODS: A diabetic mouse model was...
OBJECTIVE: To investigate the role of Membrane Metalloendopeptidase (MME) in oxidative stress and inflammation in painful diabetic neuropathy, and to explore the underlying mechanism. METHODS: A diabetic mouse model was established with streptozocin (STZ) injections. Neuropathic pain was assessed using paw withdrawal latency (PWL). Target genes related to painful diabetic neuropathy were identified using the Comparative Toxicogenomic Database (CTD), DisGeNET, and GeneCards. Protein-protein interactions between MME and the Nrf2/HO-1 signaling pathway were analyzed using the String database. The effects of MME overexpression, with or without the Nrf2 inhibitor ML385, on neuropathy were examined. Blood glucose, insulin levels, oxidative stress indicators, and inflammatory cytokines were measured. Gene expression was quantified by qRT-PCR, and protein levels were assessed by Western blot and immunohistochemistry. RESULTS: Diabetic mice showed elevated blood glucose, MDA, ROS, TNF-α, IL-1β, IL-6, and decreased serum insulin, PWL, SOD activity, and MME levels. MME interacted with Nrf2 and HO-1, which were reduced in diabetic mice. Overexpression of MME led to improved serum insulin, PWL, SOD activity, and increased Nrf2 and HO-1 levels, while reducing MDA, ROS, TNF-α, IL-1β, and IL-6. These effects were partially reversed by ML385. CONCLUSION: Overexpression of MME mitigates oxidative stress and inflammation in painful diabetic neuropathy by activating the Nrf2/HO-1 signaling pathway.
The Role of MicroRNA-200 Family in Gastrointestinal Cancers.
Li J, Pan J, Wen J … +1 more , Wang C
Curr Mol Med · 2026 Mar · PMID 41863249 · Publisher ↗
INTRODUCTION: Gastrointestinal cancers, including esophageal cancer, gastric cancer, liver cancer, pancreatic cancer, and colorectal cancer, are a major health burden worldwide, characterized by high incidence and mortal...
INTRODUCTION: Gastrointestinal cancers, including esophageal cancer, gastric cancer, liver cancer, pancreatic cancer, and colorectal cancer, are a major health burden worldwide, characterized by high incidence and mortality rates. Traditional diagnostic methods are not satisfactory. The compliance of patients with endoscopic examinations is poor, and the sensitivity and specificity of conventional tumor markers are also not high. Liquid biopsy, especially the detection of exosomal microRNAs (miRNAs), as a promising alternative method, has emerged, among which the miR-200 family has been identified as a key regulatory factor in the pathogenesis of gastrointestinal cancers. METHODS: A literature search was conducted from 2002 to 2025, and the keywords used included "gastrointestinal cancer", "miR-200 family", and "exosomal miRNA". The studies involved included those on the role of miR-200 in gastrointestinal cancers, as well as research on exosomal miR-200 as a biomarker or therapeutic target. Inclusion criteria include: original studies published in English and peer-reviewed, which explored the biological, diagnostic, prognostic, or therapeutic effects of the miR-200 family in gastrointestinal cancers, and provided the complete papers that are accessible. If the research is a review, a conference summary, an editorial, a duplicate dataset, or lacks sufficient experimental or clinical data related to miR-200, it will be excluded. This literature search was conducted in the PubMed database. After screening, a total of 248 articles were obtained, and finally, 133 studies were included in the analysis. This review adhered to the guidelines of SANRA and employed a narrative research method. The key findings were qualitatively synthesized to summarize the mechanism of miR-200 and its clinical relevance. RESULTS: MicroRNA-200 regulates the occurrence and development of gastrointestinal cancers by modulating epithelial-mesenchymal transition (EMT), angiogenesis, cancer stem cell properties, and chemotherapy resistance. Its expression in tumor tissues is closely related to clinical pathological features, prognosis, and treatment response. Furthermore, the miR-200 present in exosomes exhibits extremely high stability in circulation and specificity towards cancer. DISCUSSION: Studies have shown that miR-200 family regulates the occurrence and development of gastrointestinal cancer by targeting epithelial-mesenchymal transition, angiogenesis, and other characteristics, and its expression is related to clinicopathological characteristics and prognosis. Exosomal miR-200 family has shown good diagnostic performance in gastrointestinal malignancies. In an independent validation cohort, the AUC of combined miR-200a-3p and miR200b-3p expression in pancreatic ductal adenocarcinoma (PDAC) was 0.97, with a sensitivity of 100% and a specificity of 88%. Notably, combining this miRNA combination with CA19-9 further improved diagnostic accuracy, increasing the AUC of the combined model from 0.86 for CA19-9 alone to 0.997. In addition, miR-200c had a moderate but significant diagnostic and prognostic value for GC, with a combined AUC of 0.75, a sensitivity of 0.74, and a specificity of 0.66. Limitations such as the heterogeneity of studies and the unclear mechanism of exosome packaging can be alleviated by standardized protocols. Future studies should focus on largescale multi-center trials, in-depth exploration of molecular mechanisms, and standardization of experimental workflow. CONCLUSION: Exosomal miR-200 overcomes the limitations of traditional diagnosis and is expected to become a biomarker and therapeutic target for gastrointestinal tumors. The miR-200 family had the strongest diagnostic evidence in pancreatic ductal adenocarcinoma (AUC = 0.97, sensitivity = 100%, specificity = 88%) and gastric cancer (AUC = 0.75, sensitivity = 74%, specificity = 66%). These data highlight its translational potential as a clinically relevant biomarker for early and non-invasive gastrointestinal cancer detection. Validation in large cohorts and the development of targeted therapies will be essential to improve patient outcomes.
Development of Integrated Turbidity Spectrophotometric Biosensor System with Osmotic Fragility/DichlorophenolIndophenol Precipitation Assays for Thalassemia Red Blood Cell Screening.
Pramool P, Wanram S, Butchai K … +3 more , Charoenrat P, Pencharee S, Wanram S
Curr Mol Med · 2026 Mar · PMID 41863248 · Publisher ↗
INTRODUCTION: Thalassemia remains a major public health burden, particularly in low-resource regions where access to advanced laboratory diagnostics is limited. Although high-performance liquid chromatography (HPLC) and...
INTRODUCTION: Thalassemia remains a major public health burden, particularly in low-resource regions where access to advanced laboratory diagnostics is limited. Although high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) provide reliable hemoglobin characterization, their cost, infrastructure requirements, and turnaround time restrict large-scale screening. From a practical screening perspective, there is a clear need for a rapid, portable, and objective point-of-care (POC) approach that supports early identification and appropriate referral. METHODS: We developed an integrated turbidity spectrophotometric biosensor that quantitatively combines the osmotic fragility (OF) test and the dichlorophenolindophenol precipitation (DCIP) clear assay. The system employs a portable LEDbased spectrophotometric reader controlled by an ESP32 microcontroller, integrated with real-time web-based visualization and automated interpretation. Ninety-nine EDTA blood specimens were analyzed. Red blood cell fragility and hemoglobin stability were assessed using time-resolved absorbance slope measurements at 540 and 600 nm for OF and DCIP, respectively. Analytical reproducibility, diagnostic performance, and agreement with reference methods were evaluated. RESULTS: The biosensor demonstrated high analytical reproducibility, with mean coefficients of variation of 2.8% for OF slopes and 3.5% for DCIP slopes. Diagnostic performance was robust, yielding AUC values of 0.94 for OF and 0.90 for DCIP. An integrated decision algorithm achieved an overall concordance of 90.2% with goldstandard methods and provided preliminary interpretation within 3 minutes through a secure web-based dashboard. DISCUSSION: Quantitative integration of OF and DCIP assays within a single platform improves screening objectivity while maintaining rapid turnaround, supporting decentralized and point-of-care testing. CONCLUSION: This integrated turbidity biosensor offers a rapid and scalable POC solution for preliminary thalassemia screening in underserved settings. Future development will focus on mobile integration, secure linkage with public health systems, and incorporation of additional hematologic or molecular parameters to further enhance diagnostic confidence.
Microbiota-driven Immunopathogenesis in Systemic Lupus Erythematosus: Cross-site Mechanisms and Intervention Strategies.
Feng S, Huang Q
Curr Mol Med · 2026 Mar · PMID 41863247 · Publisher ↗
Systemic lupus erythematosus (SLE) is a complex autoimmune disease whose pathogenesis involves intricate interactions with the human microbiota. Accumulating evidence reveals significant compositional and functional dysb...
Systemic lupus erythematosus (SLE) is a complex autoimmune disease whose pathogenesis involves intricate interactions with the human microbiota. Accumulating evidence reveals significant compositional and functional dysbiosis in the gut, oral, skin, and vaginal microbiota of SLE patients compared to healthy individuals. These dysbioses actively contribute to disease development and progression through a multitude of mechanisms. These include impaired epithelial barrier integrity, exemplified by the "leaky gut" phenomenon, which facilitates the translocation of microbial antigens. Molecular mimicry, where microbial antigens share structural similarities with host self-antigens, triggers the production of cross-reactive autoantibodies. Furthermore, dysregulated production of microbial metabolites, such as short-chain fatty acids, tryptophan derivatives like tryptamine, and histamine, directly modulates host immune cell function, promotes inflammatory responses, and influences epigenetic regulation. The causal role of specific microbiota in SLE is substantiated by experimental models, including fecal microbiota transplantation studies where transfer of SLE-associated microbiota can recapitulate autoimmune features in recipient germ-free mice, and mono-colonization with pathobionts like Ruminococcus gnavus or Staphylococcus aureus can drive specific aspects of the disease. This growing understanding has paved the way for novel microbiota-targeting interventions. Strategies such as dietary modifications, probiotic and prebiotic supplementation, and fecal microbiota transplantation show considerable promise in preclinical and early clinical studies for restoring microbial homeostasis, rebalancing dysregulated immune responses, and alleviating disease activity. However, challenges in patient-specific variability, understanding precise mechanisms, and ensuring longterm safety remain. Future research must focus on delineating detailed causal pathways, validating efficacy in large-scale trials, and ultimately developing personalized microbiota-targeting interventions to improve SLE management and patient outcomes.
Dynamic Changes of Extracellular Matrix in Sepsis: A Review.
Fu M, Xu W, Zhao J … +3 more , Fu S, Fu S, Ma L
Curr Mol Med · 2026 Feb · PMID 41742611 · Publisher ↗
During the pathogenesis of sepsis, extracellular matrix (ECM) impairment represents a critical pathological hallmark. The ECM not only plays pivotal roles in maintaining tissue architecture and physiological functions, b...
During the pathogenesis of sepsis, extracellular matrix (ECM) impairment represents a critical pathological hallmark. The ECM not only plays pivotal roles in maintaining tissue architecture and physiological functions, but also actively participates in cellular signaling transduction and tissue repair mechanisms. Sepsisinduced systemic inflammatory responses and oxidative stress provoke ECM component degradation and structural remodeling, which, in turn, activate multiple intracellular and intercellular signaling cascades. Bioactive fragments derived from ECM degradation can function as signaling ligands that bind to specific cell surface receptors, triggering downstream pathways that regulate critical cellular processes, including survival, proliferation, migration, and inflammatory activation. The sustained activation of these signaling networks exerts profound pathophysiological consequences, potentially leading to vascular endothelial dysfunction, dysregulated immune cell hyperactivation, and coagulation system abnormalities. Furthermore, these signaling pathways mediate essential regulatory functions during the tissue remodeling phase in late-stage sepsis. While this dynamic ECM remodeling may facilitate tissue repair and regeneration, persistent dysregulation could result in maladaptive fibrosis and permanent organ dysfunction. Collectively, the ECM demonstrates multifaceted involvement in sepsis pathophysiology through its regulatory effects on cellular signaling, functional modulation, and tissue remodeling processes. This article systematically synthesizes current knowledge regarding ECM dynamics in sepsis pathogenesis.
Functional Roles of Non-Coding RNAs in Graves' Disease.
Anbiyaee O, Salehi AM, Jaberian Asl B … +3 more , Jamshidi F, Ghaedrahmati F, Farzaneh M
Curr Mol Med · 2026 Feb · PMID 41716051 · Publisher ↗
Graves' disease (GD) is a disorder marked by an enlarged and overactive thyroid gland (Graves' hyperthyroidism), ocular abnormalities (Graves' orbitopathy; GO), and localized dermopathy (pretibial myxoedema; PTM). It is...
Graves' disease (GD) is a disorder marked by an enlarged and overactive thyroid gland (Graves' hyperthyroidism), ocular abnormalities (Graves' orbitopathy; GO), and localized dermopathy (pretibial myxoedema; PTM). It is recognized as the most common cause of hyperthyroidism worldwide. Patients with GD most frequently exhibit elevated thyroid hormone secretion from thyroid cells as a result of autoantibodies acting as thyroid-stimulating hormone receptor (TSHR) agonists. Numerous investigations have examined the elements that contribute to the pathogenesis of GD, focusing on different components, such as molecular factors like non-coding RNAs (ncRNAs). NcRNAs represent a type of RNA transcript that, while not encoding proteins, are essential in the regulation of numerous aspects of cellular biology. NcRNAs include major groups, such as circular RNAs (circRNAs), long noncoding RNAs (lncRNAs), and small non-coding RNAs (sncRNAs), all of which are garnering increasing interest in the scientific community. This review will provide a comprehensive analysis of the function of ncRNAs in the development, diagnosis, and treatment of GD, and investigate the latest research in this area.
Alterations in the Expression of Toll-Like Receptors (TLRs) 3, 4, and 7 in Patients with COVID-19: The Role of Disease Severity and Gender.
Ghoreshi ZA, Sharif-Zak M, Asadikaram G … +8 more , Abbasi-Jorjandi M, Afsharipur A, Seyedi F, Reshidinejad H, Kazemiarababadi M, Khajepour F, Arefinia N, Abolhassani M
Curr Mol Med · 2026 Feb · PMID 41664376 · Publisher ↗
<P> Introduction: The expression dynamics of Toll-like receptors (TLRs) in response to SARS-CoV-2, particularly regarding disease severity, remain poorly understood. This study aimed to investigate the gene expression of...
<P> Introduction: The expression dynamics of Toll-like receptors (TLRs) in response to SARS-CoV-2, particularly regarding disease severity, remain poorly understood. This study aimed to investigate the gene expression of TLR3, TLR4, and TLR7 in COVID-19 patients and correlate them with disease severity and gender. </P> <P> Methods: This case-control study enrolled 470 COVID-19 patients (categorized as moderate, severe, and critical) and 100 healthy controls. The mRNA expression levels of these genes in peripheral blood leukocytes were quantified using RT-qPCR. </P> <P> Results: Expression of all three TLRs was significantly higher in patients than in the control group. Overall, male patients exhibited higher expression than females. Notably, a significant decrease in TLR3, TLR4, and TLR7 expression was observed in the critical group compared with the moderate and severe groups. </P> <P> Discussion: This paradoxical downregulation of TLRs in critical patients, reported for the first time in such a large cohort (N=470), aligns with reports of 'immunoparalysis' or 'immune exhaustion' observed in other severe inflammatory conditions. This phenomenon might represent a negative feedback mechanism to prevent overwhelming systemic inflammation, although it may concurrently compromise pathogen clearance. </P> <P> Conclusion: The findings suggest that while TLR expression is upregulated in COVID-19, its downregulation in critical stages may be associated with an unfavorable disease outcome. Therefore, TLR expression levels could be considered potential biomarkers for identifying patients at risk of progressing to the critical phase of the disease.
LncRNA HULC/miR-556-5p Axis Attenuates Ang II-Induced Cardiac Microvascular Endothelial Cell Dysfunction by Suppressing the AMPK/FOXO3 Pathway.
Hao Y, Fu M, Wang Z
Curr Mol Med · 2026 Jan · PMID 41603176 · Publisher ↗
INTRODUCTION: This study aimed to investigate the regulatory mechanism of the LncRNA HULC/miR-556-5p axis in endothelial cell injury associated with heart failure and its impact on endothelial cell function. Specifically...
INTRODUCTION: This study aimed to investigate the regulatory mechanism of the LncRNA HULC/miR-556-5p axis in endothelial cell injury associated with heart failure and its impact on endothelial cell function. Specifically, we explored how HULC interacts with miR-556-5p to modulate cell survival, apoptosis, inflammation, and autophagy in response to Ang II-induced injury. METHODS: Human cardiac microvascular endothelial cells (HCMECs) were utilized as the study model. Ang II-induced HCMEC injury was simulated by treating cells with 100 nM Ang II for 24 hours. The expression levels of HULC, miR-556-5p, and related proteins were assessed using techniques, such as real-time quantitative PCR and Western blot. Cell apoptosis was detected using flow cytometry, and inflammatory cytokine release (TNF-α, IL-1β, and IL-6) was analyzed via ELISA. Cell viability was assessed using MTT assays. Immunoblotting was employed to evaluate the phosphorylation status of key signaling molecules, including AMPK and FOXO3. RESULTS: We observed a crucial role of the LncRNA HULC/miR-556-5p axis in Ang IIinduced HCMEC injury. Overexpression of HULC significantly suppressed miR-556-5p activity, thereby reducing cell apoptosis and the release of inflammatory cytokines while promoting cell survival. Further experimental results indicated that miR-556-5p regulated cell function by reducing the expression level of FOXO3 and modulating the AMPK signaling pathway. Additionally, miR-556-5p markedly decreased cellular autophagy levels, further supporting its regulatory role in endothelial cell injury associated with heart failure. CONCLUSION: This study elucidates the important role of the LncRNA HULC/miR-556- 5p axis in endothelial cell injury associated with heart failure. Our findings provide new insights into the pathophysiological mechanisms of heart failure and highlight the potential therapeutic value of targeting this axis to improve endothelial cell function.
Nanolayered Topsheet Integration for Enhanced Antimicrobial Properties in Sanitary Napkins.
A H, K S, Deepika B … +5 more , Thirumalai A, P S SS, Perumal I, Girigoswami A, Girigoswami K
Curr Mol Med · 2026 Jan · PMID 41572758 · Publisher ↗
INTRODUCTION: Menstrual hygiene practices are a critical health concern, and if neglected, they may lead to reproductive tract infections (RTIs), toxic shock syndrome, and other vaginal diseases. To prevent these conditi...
INTRODUCTION: Menstrual hygiene practices are a critical health concern, and if neglected, they may lead to reproductive tract infections (RTIs), toxic shock syndrome, and other vaginal diseases. To prevent these conditions, antiseptic and antibacterial properties must be incorporated into sanitary napkins. METHODS: In this study, nanolayered topsheets were synthesized by embedding silver nanoparticles (AgNPs) into PVA in Aloe vera extract, which was then coated onto a non-woven fabric. The polymer-entrapped AgNPs in Aloe vera (AgNPs + PVA + Aloe vera) were characterized using UV-visible spectrometry, dynamic light scattering (DLS), zeta potential, FTIR, and SEM analyses. RESULTS: The release kinetics of AgNPs from the coated fabric were studied in simulated vaginal fluid (SVF), showing an initial burst release followed by sustained release. The toxicity of the released nanosilver was evaluated both in vitro using A375 cells and in vivo using zebrafish embryos, establishing a safe dose of 3 μM. The antimicrobial effect of the coated fabric was tested against S. aureus and E. coli, showing clear zones of inhibition. DISCUSSION: The AgNPs and the coated fabric demonstrated comparable antimicrobial activity. CONCLUSION: This product has potential for use in coating sanitary napkins to provide skin-soothing and antimicrobial effects.
Single-cell Sequencing Reveals Key Biological Insights into Intervertebral Disc Development and Degeneration.
Yu C, Yang W, Wang Y … +1 more , Zhang Y
Curr Mol Med · 2026 Jan · PMID 41572757 · Publisher ↗
Intervertebral disc degeneration (IDD) is a common spinal disease that imposes a significant economic burden on healthcare systems. Understanding the biological processes involved in IDD development and degeneration is c...
Intervertebral disc degeneration (IDD) is a common spinal disease that imposes a significant economic burden on healthcare systems. Understanding the biological processes involved in IDD development and degeneration is critical for developing potential therapeutic approaches. Single-cell RNA sequencing (scRNAseq) technology has revolutionized our understanding of cellular heterogeneity at the single-cell level and provided profound insights into the transcriptional landscape of IDD. This review provides an overview of research progress on the cellular biological characteristics of IDD occurrence and degeneration using scRNA-seq. It systematically summarizes the applications and key findings of scRNA-seq in subtyping cell populations, detecting transcriptomic changes, regulating signaling pathways, and elucidating cell-cell interactions in IDD. Additionally, it emphasizes the potential role of scRNA-seq in maintaining and repairing intervertebral disc tissues, from both preventive and therapeutic perspectives. In summary, this study underscores the extensive application of scRNA-seq in degenerative disc research and provides a foundation for future investigations and potential treatment strategies.
Neonatal Anaesthesia and Neuronal Injury: Molecular Mechanisms and Insights.
Tan RE, Ko AXY, Tan KE … +5 more , Ngai ZN, Chye SM, Ling APK, Salvamani S, Koh RY
Curr Mol Med · 2026 Jan · PMID 41572756 · Publisher ↗
Despite widespread use of general anaesthesia (GA) in neonatal procedures, its effects on the developing brain are still not fully understood, raising ongoing questions in both research and clinical practice. Experimenta...
Despite widespread use of general anaesthesia (GA) in neonatal procedures, its effects on the developing brain are still not fully understood, raising ongoing questions in both research and clinical practice. Experimental studies have demonstrated that GA can cause neuronal cell injury, and neonates may be vulnerable due to their physiological immaturity, necessitating exact dosing and constant monitoring. To optimise anaesthesia protocols and minimise risks in this vulnerable population, it is imperative to thoroughly evaluate the mechanisms underlying anaesthesia-induced neuronal cell damage in neonates. This review article will explore the following mechanisms: apoptosis, pyroptosis, gamma-aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA), oxidative stress and mitochondrial damage, calcium imbalance, neural circuit impairment, and neuroinflammation, with particular focus on studies utilising animal models. It will also highlight recent studies on therapeutic strategies against reducing neuronal cell damage. However, as most of these findings remain preclinical, their translational potential requires cautious interpretation. In conclusion, although current evidence highlights plausible mechanisms and emerging neuroprotective approaches, more clinical trials are needed to ensure the reliability and efficacy of the treatment strategies to confirm their effects on neonatal anaesthesia-induced cell damage.
Phosphatidylethanolamine: Structural Component and Beyond.
Pandey SK, Kulshreshtha A, Mishra A
Curr Mol Med · 2026 Jan · PMID 41572755 · Publisher ↗
Phosphatidylethanolamine (PE) is a major phospholipid in biological membranes and plays essential roles in autophagy, cell signaling, protein function, and membrane integrity. Its dynamic, conical structure supports memb...
Phosphatidylethanolamine (PE) is a major phospholipid in biological membranes and plays essential roles in autophagy, cell signaling, protein function, and membrane integrity. Its dynamic, conical structure supports membrane fluidity and curvature, which are crucial for processes such as signaling, autophagosome formation, membrane fusion, vesicle trafficking, and proper protein folding. Although PE is abundant, its significance for human health and disease has only recently come to light. Altered PE levels or disruptions in its metabolism have been associated with various conditions, including metabolic disorders such as non-alcoholic fatty liver disease (NAFLD), neurodegenerative diseases like Alzheimer's and Parkinson's, and several cancers. PE is synthesized primarily via two pathways: the CDP-ethanolamine (Kennedy) pathway and the mitochondrial phosphatidylserine decarboxylase (PSD) pathway, both of which are critical for maintaining lipid homeostasis. Advances in lipidomics now allow comprehensive profiling of PE species, facilitating the identification of disease-specific lipid biomarkers. This review expands current knowledge on the physiological roles of PE and elucidates mechanisms underlying PErelated lipid dysregulation in human disease.
Impact of Toll/Interleukin-1 Receptor Domain Protein C on Mesenchymal Stem Cells Mitochondrial Protein Expression: A Proteomic Study.
Wang Y, Fang J, Guo D … +1 more , Xia L
Curr Mol Med · 2026 Jan · PMID 41572754 · Publisher ↗
INTRODUCTION: Stem cells play a pivotal role in immunomodulation and tissue repair, and their functions can be influenced by TLR signaling. The Toll/interleukin-1 receptor domain-containing protein C (TcpC), secreted by...
INTRODUCTION: Stem cells play a pivotal role in immunomodulation and tissue repair, and their functions can be influenced by TLR signaling. The Toll/interleukin-1 receptor domain-containing protein C (TcpC), secreted by Uropathogenic Escherichia coli, can inhibit host immunity by interfering with TLR pathways. As mitochondria are crucial for stem cell function, there may be links between TcpC and mitochondrial homeostasis. METHODS: We isolated MSC mitochondria using magnetic beads coated with a monoclonal antibody against the outer mitochondrial membrane protein OMP25 and conducted a proteomic study to examine the MSC mitochondrial proteome with or without TcpC. Bioinformatics analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and proteinprotein interaction (PPI) network analysis, were employed. RESULTS: A total of 33 proteins with significant changes in abundance were identified: 4 increased in abundance, including glycolytic enzymes (Pkm [FC=1.6599, p=0.0217]) and stress response proteins (Ywhaq [FC=1.4666, p=0.04502]); and 29 decreased, mainly related to mitochondrial oxidative phosphorylation (e.g., Atp5f1e [FC=0.001, p=0.00120], Ndufa11 [FC=0.001, p=0.00674]) and protein quality control (e.g., Grpel1 [FC=0.46663, p=0.02083], Hspa9 [FC=0.48089, p=0.0435], Pitrm1 [FC=0.12764, p=0.01388]). DISCUSSION: The possible effects of TcpC on the MSC mitochondrial proteome are reported here for the first time. This information provides a clearer understanding of MSCs in the context of infectious disease and offers a scientific basis for future stem cell therapy research. CONCLUSION: TCP-C intervention leads to a series of differentially expressed proteins in MSC mitochondria, which are involved in several functional clusters, including oxidative phosphorylation, respiratory electron transport, the tricarboxylic acid cycle, glyoxylate and dicarboxylate metabolism, branched-chain amino acid catabolism, and cristae formation.
SSR2 Promotes Sorafenib Resistance Via Interacting with GPX4 to Inhibit Ferroptosis.
Song Z, Zhou M, Song X … +2 more , Jia H, Yang X
Curr Mol Med · 2026 Jan · PMID 41568502 · Publisher ↗
AIM & OBJECTIVES: Sorafenib is a first-line drug for hepatocellular carcinoma (HCC). Understanding the regulatory mechanisms of sorafenib resistance is critical to inhibit sorafenib resistance and develop novel therapeut...
AIM & OBJECTIVES: Sorafenib is a first-line drug for hepatocellular carcinoma (HCC). Understanding the regulatory mechanisms of sorafenib resistance is critical to inhibit sorafenib resistance and develop novel therapeutic strategies. Here, we aimed to study the role of SSR2 (signal sequence receptor subunit 2) in sorafenib resistance of HCC. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, and cell viability assay were used to determine the role of SSR2 in sorafenib resistance of HCC. Co-immunoprecipitation (CoIP) was used to determine the interacting protein of SSR2. RESULTS: We found SSR2 was upregulated in sorafenib-resistant HCC tissues. In addition, in HCC patients, SSR2 was associated with both poor response to sorafenib and poor clinical outcomes. Functional assay showed that SSR2 promoted sorafenib resistance in HCC cells. Mechanistically, SSR2 suppressed ferroptosis. Further analysis showed that SSR2 interacted with ferroptosis master regulator glutathione peroxidase 4 (GPX4) and increased the catalytic activity of GPX4, leading to inhibition of ferroptosis. Induction of ferroptosis could reverse the promotion effect of SSR2 overexpression on sorafenib resistance. DISCUSSION: SRR2 plays a critical role in sorafenib resistance generation. However, the detailed mechanism of SRR2 increasing the catalytic activity of GPX4 will be further studied. CONCLUSIONS: In summary, we reveal that SSR2 enhances sorafenib resistance of HCC via interacting with GPX4 and inhibiting ferroptosis, providing a potential target for HCC treatment. The molecular mechanism of GPX4-SSR2 interaction in ferroptosis will be further studied.
SLC39A8 Inhibits Ferroptosis by Regulating the Β-Catenin/TCF4/ GPX4 Signaling in Osteosarcoma.
Tang S, Tang G, Chen L … +5 more , Luo M, Huang J, Zhang Z, Wen S, Xiao Z
Curr Mol Med · 2026 Jan · PMID 41568501 · Publisher ↗
INTRODUCTION: SLC39A8 has been implicated in various cancers; however, its specific role in osteosarcoma (OS) remains poorly understood. This study aims to elucidate the functional significance of SLC39A8 in OS progressi...
INTRODUCTION: SLC39A8 has been implicated in various cancers; however, its specific role in osteosarcoma (OS) remains poorly understood. This study aims to elucidate the functional significance of SLC39A8 in OS progression. METHODS: Using qRT-PCR and Western blot analysis, we analyzed SLC39A8 expression in osteosarcoma cells. Functional assays, including CCK-8, colony formation, and transwell assays, were employed to assess the impact of SLC39A8 on cell proliferation, migration, and invasion. Ferroptosis was evaluated by measuring lipid peroxidation, labile iron pool (LIP), Fe²⁷, malondialdehyde (MDA), reactive oxygen species (ROS), glutathione (GSH), and GPX4 expression. RESULTS: Our results revealed that SLC39A8 is upregulated in osteosarcoma cells. The knockdown of SLC39A8 significantly suppressed cell proliferation, migration, and invasion while inducing ferroptosis, as evidenced by increased levels of LIP, Fe²⁷, MDA, and ROS, and decreased GSH and GPX4 expression. These effects were reversed by the ferroptosis inhibitor ferrostatin-1 (Fer-1). Furthermore, SLC39A8 overexpression activated the Wnt/β-catenin signaling pathway and upregulated GPX4 expression, effects that were abrogated by silencing β-catenin or TCF4. In vivo experiments confirmed that SLC39A8 knockdown inhibited tumor growth. DISCUSSION: SLC39A8 is a key zinc and iron transporter. Studies have reported that SLC39A8 was significantly dysregulated in some cancers and was associated with their prognosis. SLC39A8 has been identified as an iron metabolism- and ferroptosisrelated gene related to the prognosis of esophageal squamous cell carcinoma. Our study showed that SLC39A8 promotes osteosarcoma cell proliferation, migration, and invasion while suppressing ferroptosis by regulating β-catenin signaling. Our study further indicated that LF3 reversed SLC39A8-mediated ferroptosis in osteosarcoma cells by reducing GPX4 expression. Although our study shows that SLC39A8 regulates the β-catenin signaling pathway, the upstream regulatory mechanism remains to be investigated. CONCLUSION: Our findings demonstrate that SLC39A8 plays a pivotal role in osteosarcoma progression by modulating ferroptosis via the β-catenin/TCF4/GPX4 signaling pathways.
A Cuproptosis-related lncRNA Signature for Prognostic Stratification and Immunotherapeutic Implications in Lung Adenocarcinoma.
Jiang Y, Xing D, Luo K … +7 more , Guo J, Zhai Y, Li C, He X, Wang J, Wu W, Zhao Z
Curr Mol Med · 2026 Jan · PMID 41540526 · Publisher ↗
BACKGROUND: Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer, and there have been disputes over its prognostic biomarker and clinical outcome. Cuproptosis, a novel form of regulated cell...
BACKGROUND: Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer, and there have been disputes over its prognostic biomarker and clinical outcome. Cuproptosis, a novel form of regulated cell death (RCD), has been insufficiently explored in terms of its potential role in LUAD. METHODS: In this study, we developed a machine learning-based integrative procedure for constructing a consensus cuproptosis-related lncRNA signature (CTLNS) using TCGA data and validated it with external datasets. RESULTS: The CTLNS was identified as an independent predictor of overall survival, showing stable and accurate performance across multiple cohorts. Patients classified into high- and low-risk groups exhibited significant differences in survival outcomes. Functional analyses revealed that the low-risk group was enriched in DNA replication and immune-related pathways, while the high-risk group was associated with oncogenic signaling and cell cycle regulation. Notably, high-risk patients showed increased sensitivity to several chemotherapy agents, including Docetaxel, Cisplatin, Gefitinib, and Paclitaxel, while low-risk patients were more responsive to Nilotinib. CONCLUSION: These findings suggest that CTLNS is a reliable biomarker for prognostic prediction and treatment stratification in LUAD, offering potential utility in personalized therapy.
Adiponectin Ameliorates Intrauterine Adhesion-Related Endometrial Inflammation and Fibrotic Changes by Downregulating the NLRP3/IL-1β/TGF-β1 Axis.
Yang W, Li Q, Zhang Y … +1 more , Zhi Z
Curr Mol Med · 2025 Nov · PMID 41293920 · Publisher ↗
INTRODUCTION: Intrauterine Adhesions (IUA), a common gynecological condition often caused by infection or endometrial injury, significantly impact women's reproductive and mental health. Its unclear pathogenesis hinders...
INTRODUCTION: Intrauterine Adhesions (IUA), a common gynecological condition often caused by infection or endometrial injury, significantly impact women's reproductive and mental health. Its unclear pathogenesis hinders the development of effective treatments. Adiponectin, a bioactive protein with anti-inflammatory and antifibrotic properties, may offer therapeutic potential. This study investigates adiponectin's effects and mechanisms in IUA to inform new clinical strategies.. METHODS: Endometrial tissues from IUA patients and controls were analyzed via immunohistochemistry to assess NLRP3, IL-1β, TGF-β1, and adiponectin expression. A human IUA cell model was established by stimulating human endometrial stromal cells (HESCs) with TGF-β1 (10 ng/ml, 48 hours). Interventions using the NLRP3 inhibitor MCC950, activator nigericin sodium salt, and adiponectin were applied. Protein and mRNA expression levels of NLRP3, IL-1β, TGF-β1, α-SMA, and COL1A1 were evaluated via Western blot and RT-qPCR. In vivo, IUA model rats were treated with adiponectin, and uterine morphology, gland count, collagen deposition, and inflammatory/fibrotic markers were analyzed. RESULTS: NLRP3, IL-1β, and TGF-β1 expression were significantly upregulated in IUA patient tissues, while adiponectin was downregulated (P<0.05). In the TGF-β1-induced IUA cell model, NLRP3 inhibition with MCC950 reduced IL-1β and TGF-β1 levels, whereas NLRP3 activation with nigericin increased them. Adiponectin intervention significantly decreased NLRP3, IL-1β, TGF-β1, α-SMA, and COL1A1 expression in vitro (P<0.05). In IUA rats, adiponectin improved uterine morphology, increased endometrial glands, reduced collagen fiber deposition, and downregulated NLRP3, IL- 1β, and TGF-β1 expression (P<0.05). DISCUSSION: Adiponectin alleviates endometrial inflammation and fibrosis in IUA, potentially by modulating the NLRP3/IL-1β/TGF-β1 signaling pathway. These findings highlight adiponectin's role in mitigating IUA progression and provide a theoretical basis for its clinical applications. CONCLUSION: Adiponectin reduces inflammation and fibrosis in IUA by suppressing the NLRP3/IL-1β/TGF-β1 axis, offering new insights for IUA treatment strategies.
Preface.
Guttman A
Curr Mol Med · 2026 · PMID 41293919 · Publisher ↗
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