Current Molecular Medicine[JOURNAL]
Sun
200 papers
Corrigendum to: Sortilin as a Culprit in the Atherosclerosis Plaque Progression: Evidence from Clinical and Experimental Studies.
Cheng G, Liu J, Zhang H … +3 more , Cui Y, Xu S, Wang L
Curr Mol Med · 2026 · PMID 42370591 · Publisher ↗
It has come to our attention that in the published version of this article [1], reference [86] was cited erroneously; this has now been corrected. The original article can be found online at: https://www.eurekaselect.com...
It has come to our attention that in the published version of this article [1], reference [86] was cited erroneously; this has now been corrected. The original article can be found online at: https://www.eurekaselect.com/article/145963 Details of the correction are as follows: Original: These contradictory reports regarding the sortilin function in lipid metabolism may result from variations in employed animal models or lipid metabolic milieu. Once the intracellular level of apoB-100 is elevated, sortilin may primarily act as "the degrader," whereby sortilin can target VLDL to the lysosomal degradation and thus reduce the secretion of VLDL particles [28]. Oppositely, in situations of reduced expression of apoB-100, like in the DKO mouse model, sortilin can also exhibit "the chaperone" activity and assist the formation and secretion of VLDL particles [86]. According to such a theory, the impacts of sortilin on liver lipid metabolism depend on the physiological demands and the metabolic context. Moreover, sortilin can target lipid-related proteins and regulate their expression and functions, consequently influencing lipid metabolism. Thus, it is essential to consider whether deficiency or overexpression of the SORT1 gene or sortilin protein disrupts the expression of other lipid genes and corresponding proteins. Corrected: These contradictory reports regarding the sortilin function in lipid metabolism may result from variations in employed animal models or lipid metabolic milieu. Once the intracellular level of apoB-100 is elevated, sortilin may primarily act as "the degrader," whereby sortilin can target VLDL to the lysosomal degradation and thus reduce the secretion of VLDL particles [28]. Oppositely, in situations of reduced expression of apoB-100, like in the DKO mouse model, sortilin can also exhibit "the chaperone" activity and assist the formation and secretion of VLDL particles [36]. According to such a theory, the impacts of sortilin on liver lipid metabolism depend on the physiological demands and the metabolic context. Moreover, sortilin can target lipid-related proteins and regulate their expression and functions, consequently influencing lipid metabolism. Thus, it is essential to consider whether deficiency or overexpression of the SORT1 gene or sortilin protein disrupts the expression of other lipid genes and corresponding proteins.
Dynamic Expression of Fibroblast Activation Protein (FAP) During Chronic Pancreatitis (CP) Progression in Mice and Evaluation of FAP-targeted Tracers for Early CP Diagnosis.
Zhang XL, Xu XD, Ma XK … +5 more , Xiao W, Qian JP, Yang WJ, Xu H, Zhang GW
Curr Mol Med · 2026 Jun · PMID 42337889 · Publisher ↗
INTRODUCTION: Currently, effective methods for the early diagnosis of Chronic Pancreatitis (CP) remain limited. PANCREATIC STELLATE CELLS (PSCs) in pancreatitis are critical drivers of CP progression, and PSCs are known...
INTRODUCTION: Currently, effective methods for the early diagnosis of Chronic Pancreatitis (CP) remain limited. PANCREATIC STELLATE CELLS (PSCs) in pancreatitis are critical drivers of CP progression, and PSCs are known to overexpress Fibroblast Activation Protein (FAP) in inflamed pancreatic tissue. This study aims to investigate the correlation between the dynamic changes in FAP expression by PSCs and CP progression, and to evaluate the feasibility of three FAP inhibitor (FAPI)-based tracers for early CP diagnosis. METHOD: Caerulein-treated PRSS1 transgenic mice (PRSS1Tg) were categorized into four groups based on the development stage of CP. The pancreatic pathology was observed using HE and Masson staining. Moreover, immunohistochemistry, immunofluorescence, and qRT-PCR were employed to further analyze the pancreas. Additionally, near-infrared in vivo fluorescence imaging was performed with ICG-FAPI- 04, whereas Micro-PET/CT was performed with 68Ga-FAPI-04 and 18F-FAPI-42. The results were subsequently observed and analyzed. RESULTS: Experiments revealed that FAP was overexpressed in CP, with its expression peaking at 2 weeks. In vivo near-infrared imaging using ICG-FAPI-04 failed to effectively assess pancreatic morphology and fibrosis at the 2-week time point in the CP model mice. In micro-PET/CT evaluations of CP model mice at two weeks, 18FFAPI- 42 demonstrated superior visualization of pancreatic morphology and fibrosis compared to 68Ga-FAPI-04. DISCUSSION: The near-infrared probe ICG-FAPI-04 shows limited efficacy, but its performance could be improved by increasing hydrophilicity or adopting NIR-II imaging. In comparison, FAPI-based PET/CT-especially using 18F-FAPI-42-offers clear visualization of pancreatic morphology, positioning it as a highly promising tool for CP detection. CONCLUSION: This study demonstrated dynamic FAP expression during CP progression. FAP-targeted tracers were shown to sensitively visualize the pancreatic morphology reflecting fibrosis severity, validating their feasibility for early CP diagnosis.
Causal Relationship Between 91 Inflammatory Factors and Gastritis: A Two-Sample Bidirectional Mendelian Randomization Study.
Wang T, Lin L
Curr Mol Med · 2026 Jun · PMID 42316505 · Publisher ↗
INTRODUCTION: Emerging evidence from recent pathological investigations has demonstrated that inflammation plays a critical role in the progression of gastrointestinal diseases. However, the causal relationships between...
INTRODUCTION: Emerging evidence from recent pathological investigations has demonstrated that inflammation plays a critical role in the progression of gastrointestinal diseases. However, the causal relationships between inflammation and gastritis still lack further validation. METHODS: Mendelian Randomization (MR) was used to evaluate the causal effects of inflammatory factors on gastritis. The datasets of 91 inflammatory factors were obtained from the Genome-Wide Association Study (GWAS) database, and the genetic datasets of Acute Gastritis (AG) and Chronic Gastritis (CG) were obtained from the GWAS database and the FinnGen database, respectively. Heterogeneity and pleiotropy were assessed with Cochran's Q test and MR-Egger's intercept test, respectively. RESULTS: After accounting for heterogeneity and horizontal pleiotropy, MR analysis identified Axin-1, C-X-C motif chemokine 10 (CXCL10), and Fms-related tyrosine kinase 3 ligand to be significantly associated with acute gastritis, while linking CXCL10, glial cell line-derived neurotrophic factor, Leukemia Inhibitory Factor Receptor (LIFR), hepatocyte growth factor, and fibroblast growth factor 19 to chronic gastritis. Furthermore, reverse MR analysis revealed that CG could significantly downregulate the levels of Interleukin-2 receptor subunit beta, Interleukin-15 receptor subunit alpha, Interleukin-20 receptor subunit alpha, LIFR, and Interleukin-1-alpha. DISCUSSION: This study found that AG and CG were associated with distinct inflammatory factors and that CG could reverse the levels of inflammatory factors. CXCL10 and LIFR may be potential biomarkers for gastritis. CONCLUSION: This study systematically identified causal relationships between inflammatory factors and gastritis. The identified inflammatory factors offer new insights into potential targets for gastritis.
Therapeutic Potential of Pistacia Atlantica Gum in Aspirin-Induced Peptic Ulcers: A Dose-Dependent Approach to Mucosal Protection and Hepatorenal Safety.
Sayehmiri K, Heidarizadi S, Sayehmiri K … +1 more , Azizi M
Curr Mol Med · 2026 Jun · PMID 42316504 · Publisher ↗
INTRODUCTION: Aspirin-induced peptic ulcers present a major clinical challenge, driving the search for safer, natural gastroprotective agents. This study evaluated the therapeutic potential and safety of Pistacia atlanti...
INTRODUCTION: Aspirin-induced peptic ulcers present a major clinical challenge, driving the search for safer, natural gastroprotective agents. This study evaluated the therapeutic potential and safety of Pistacia atlantica gum (PAG) in a rat model of aspirin-induced gastric damage. MATERIALS AND METHODS: Forty-nine male Wistar rats were divided into seven groups (n=7): normal control, aspirin control, aspirin + vehicle, aspirin + PAG (3, 6, or 12 mg/kg), and aspirin + sucralfate (70 mg/kg, positive control). Ulcers were induced by oral aspirin (200 mg/kg for 3 days). Treatments were administered for two weeks. Assessments included ulcer scoring, serum biochemical markers (ALT, AST, ALP, GGT, BUN, creatinine), oxidative/antioxidant status (MDA, SOD), inflammatory cytokines (IL-6, TNF-α), and blinded histopathological evaluation. RESULTS: PAG exhibited a dose-dependent reduction in ulcer severity, with the 12 mg/kg dose achieving efficacy comparable to sucralfate. Biochemically, PAG 12 mg/kg significantly ameliorated aspirin-induced hepatotoxicity (reduced ALT, AST, ALP, and GGT) and nephrotoxicity (reduced BUN and creatinine), surpassing sucralfate, which showed no renal benefit. PAG treatment also mitigated oxidative stress (increased SOD, decreased MDA) and suppressed pro-inflammatory cytokines (IL-6, TNF-α). Histopathological analysis confirmed significant mucosal preservation in PAG-treated groups. DISCUSSION: The study highlights PAG's multifaceted therapeutic profile, aligning with its traditional use in Kurdish medicine. Its efficacy is likely associated with phytochemicals such as α-pinene and flavonoids, which are suggested to modulate oxidative stress, inflammation, and apoptosis pathways. Notably, PAG may offer a safer profile, as it lacks nephrotoxic effects and exhibits hepatorenal protective properties. CONCLUSION: PAG emerges as a potent natural remedy for aspirin-induced ulcers, combining mucosal protection with systemic safety.
Identification and Characterization of MicroRNAs Associated with Borax-mediated Anti-tumor Activity through High-throughput Technology.
Zhou W, Sheng F, Zhou J … +10 more , Wang J, Huang X, Chen Q, Li J, Li H, Liu M, Zhu J, Liu J, Wei Y, Wu L
Curr Mol Med · 2026 Jun · PMID 42304903 · Publisher ↗
OBJECTIVE: The primary aim of this study was to explore the involvement of miRNAs in the anti-tumor effects of borax through high-throughput sequencing analysis. METHODS: Total RNA was extracted and purified from HepG2 c...
OBJECTIVE: The primary aim of this study was to explore the involvement of miRNAs in the anti-tumor effects of borax through high-throughput sequencing analysis. METHODS: Total RNA was extracted and purified from HepG2 cells treated with 4 mM borax for 2 or 24 hours. The samples were subjected to microarray analysis using a human miRNA array. Differentially expressed miRNAs were identified through a volcano plot and heatmap analysis and validated using quantitative PCR. A proteinprotein interaction (PPI) network was constructed, and hub genes were identified using Cytoscape software. RESULTS: Exposure to borax significantly altered miRNA expression levels in HepG2 cells. After 2 or 24 hours of borax treatment, 14 miRNAs were upregulated, respectively, while 3 miRNAs were downregulated compared to the control group (≥2- fold change, P<0.05). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that the target genes of differentially expressed miRNAs were primarily involved in the MAPK, TGF-β, and NFκB signaling pathways in the 2-hour treatment group. In contrast, the 24-hour treatment group showed involvement in the Ras signaling pathway, the forkhead box O signaling pathway, and cellular senescence. PPI network analysis identified NACC2, CACNB1, and FZD6 as hub genes in the 2-hour treatment group, while CDK6, BCL-2, IGF1R, BTG2, AGO2, and DLGAP3 were identified as hub genes in the 24-hour treatment group. DISCUSSION: The findings suggested that the anti-tumor effects of borax may be associated with changes in miRNA expression. CONCLUSION: This study established a potential miRNA-mRNA regulatory network related to tumor biology, providing a comprehensive understanding of the molecular mechanisms and offering new therapeutic targets for liver cancer.
Broad-Spectrum Vaccines: Challenges and Opportunities (A Systematic Review).
Pandey SK, Singh S
Curr Mol Med · 2026 Jun · PMID 42304743 · Publisher ↗
BACKGROUND: Though advances in technologies have created an arena for multiple vaccinology platforms, the world population is still facing health challenges from the deadliest pathogens with a high mutation rate and thei...
BACKGROUND: Though advances in technologies have created an arena for multiple vaccinology platforms, the world population is still facing health challenges from the deadliest pathogens with a high mutation rate and their tremendous ability of immune evasion. Presently, there is a constant exigence to shift the vaccine development efforts from traditional vaccines to broad-spectrum vaccines for the effective prevention of contagious diseases. MATERIALS AND METHODS: Using several databases, a comprehensive systematic review of the literature pertinent to this article's discussion was carried out. RESULTS: The present review article aims to provide a comprehensive understanding of the key characteristics and benefits of broad-spectrum vaccines over conventional vaccines. Further, it unveils the diverse range of broad-spectrum vaccines that have been developed so far, in addition to those that are currently under pre-clinical and clinical studies. Along with the illustration of the obstacles and possibilities concerned with their safety profile and viability of development, it also examines their potential for further research. DISCUSSION: The development of broad-spectrum vaccines benefits greatly from the combination of several immunisation strategies. The scope and effectiveness of broadspectrum vaccinations have been shown to be greatly increased by combining various vaccination tactics, such as using multiple immunisation techniques, multivalent antigens, or heterologous boosters. CONCLUSION: The development and practical validation of broad-spectrum vaccines have been impeded thus far by biological complexity (rapid pathogen evolution, immune imprinting, host variability), logistical limitations, and regulatory frameworks intended for strain-specific products, leaving the majority of candidates at preclinical stages. To turn promising ideas into gradual, population-level protection, policy support, and focused research improving evaluation techniques, altering regulatory pathways, and advancing mRNA, multiepitope, and T-cell approaches are required.
Immunometabolic Reprogramming: A New Frontier in Cancer Immunotherapy.
Mohammadi S, Darweesh M, Rahmati M … +3 more , Al-Hamadani M, Ahmadaghdami M, Al-Harrasi A
Curr Mol Med · 2026 Jun · PMID 42300295 · Publisher ↗
The interaction between cellular metabolism and immune function, termed immunometabolism, has been regarded as a crucial determinant of anti-tumor immunity and the efficacy of cancer immunotherapy. Understanding the meta...
The interaction between cellular metabolism and immune function, termed immunometabolism, has been regarded as a crucial determinant of anti-tumor immunity and the efficacy of cancer immunotherapy. Understanding the metabolic dependencies and vulnerabilities of various immune cell subsets and cancer cells is enabling researchers to study novel therapeutic strategies. These strategies aim to reprogram the metabolic landscape of the TME to enhance stronger anti-tumor immune responses and overcome resistance to current immunotherapies. This review provides a comprehensive overview of the fundamental principles of immunometabolism, detailing the key metabolic pathways and regulators in immune and cancer cells. We explore the distinct metabolic profiles of various immune cell subsets and how they are altered during an anti-tumor response. Furthermore, we discuss the metabolic hallmarks of cancer cells, considering variations across different cancer types. Then, we discuss how current immunotherapies, such as checkpoint inhibitors and CAR-T cell therapy, impact and are influenced by cellular metabolism. Finally, we highlight promising therapeutic opportunities for targeting immunometabolism, including metabolic inhibitors, modulators, and combination strategies. This review aims to introduce immunometabolic reprogramming as a new frontier to enhance the efficacy of cancer immunotherapy and improve patient outcomes.
Study on the Cytotoxic Effects, Apoptosis Induction, Treatment Resistance, and Inflammation Caused by a Gold(III) Complex Containing 3,4-diaminobenzophenone and 2,3-butanedione Monoxime on the Esophageal Cancer Cell Line KYSE-30.
Lu X, Majd MH, Shahraki S … +1 more , Li S
Curr Mol Med · 2026 Jun · PMID 42283168 · Publisher ↗
BACKGROUND: Given the known therapeutic properties of gold compounds such as auranofin, this study aimed to evaluate the anticancer potential of a newly synthesized gold(III) Schiff base complex. We hypothesized that thi...
BACKGROUND: Given the known therapeutic properties of gold compounds such as auranofin, this study aimed to evaluate the anticancer potential of a newly synthesized gold(III) Schiff base complex. We hypothesized that this complex could selectively induce apoptosis in cancer cells while minimizing inflammatory responses in normal cells. METHODS: A gold(III) complex bearing a tetradentate Schiff base ligand was synthesized, and its cytotoxicity was assessed using MTT assay and sulforhodamine B staining. KYSE-30 esophageal cancer cells and NIH/3T3 normal fibroblasts were treated with the complex and compared to cisplatin. Gene expression analysis was performed to evaluate apoptotic and inflammatory genes. RESULTS: The gold(III) Schiff base complex significantly inhibited KYSE-30 cell proliferation more effectively than cisplatin after 48 hours. Unlike cisplatin, it did not induce cytotoxicity in NIH/3T3 cells. The complex elevated the BAK1/Bcl-xL ratio by 2.22-fold, suggesting activation of the intrinsic mitochondrial apoptotic pathway, which was not observed with cisplatin. It also downregulated the anti-apoptotic Bcl-xL gene (0.662-fold) and the resistance-associated AKT1 gene (0.0544-fold). Both the gold(III) Schiff base complex and cisplatin activated the extrinsic apoptotic pathway via Caspase-3. Importantly, neither compound induced TNF-α expression, indicating no inflammatory response in normal cells. DISCUSSION: These findings demonstrate that the gold(III) Schiff base complex selectively targets esophageal cancer cells through dual apoptotic pathways while sparing normal cells from cytotoxicity and inflammation. Its ability to suppress resistance-related genes further highlights its therapeutic promise. CONCLUSION: The gold(III) Schiff base complex represents a compelling alternative to cisplatin, offering enhanced anticancer efficacy, reduced toxicity to normal cells, and minimal inflammatory activation. Further investigation into its clinical potential is warranted.
GDF15 Aggravates Sepsis-Induced Coagulopathy and is Associated with PI3K/AKT/mTOR Signaling Changes.
Wang L, Ji X, Lu Q … +1 more , Dong S
Curr Mol Med · 2026 Jun · PMID 42261171 · Publisher ↗
INTRODUCTION: The study was designed to explore the role of Growth Differentiation Factor 15 (GDF15) and its underlying mechanisms in coagulation dysfunction, the inflammatory response, and multi-organ damage using a rat...
INTRODUCTION: The study was designed to explore the role of Growth Differentiation Factor 15 (GDF15) and its underlying mechanisms in coagulation dysfunction, the inflammatory response, and multi-organ damage using a rat model of cecal ligation and puncture (CLP)-induced sepsis. METHODS: A CLP-induced sepsis model was established in Sprague-Dawley rats. Adenovirus vectors were used to overexpress or knockdown GDF15. A PI3K inhibitor (LY294002) was administered to specific groups. Serum levels of GDF15, apoptosis markers (cleaved-caspase3), endothelial injury markers (syndecan-1, heparan sulfate), coagulation markers (D-dimer), inflammatory cytokines (IL-6, TNF-α), and PI3K/AKT/mTOR phosphorylation were measured by ELISA. Coagulation parameters and platelet counts were assessed. Organ damage was evaluated via H&E staining of the liver, heart, and kidneys. RESULTS: GDF15 levels were significantly elevated in CLP rats. High GDF15 levels were associated with increased cleaved-caspase3, syndecan-1, heparan sulfate, Ddimer, IL-6, and TNF-α; prolonged APTT, PT, and TT; decreased platelet count and fibrinogen (FIB); aggravated multi-organ damage; and enhanced PI3K, AKT, and mTOR phosphorylation. Silencing GDF15 or inhibiting PI3K with LY294002 reversed these effects, whereas GDF15 overexpression exacerbated them. The detrimental effects of GDF15 overexpression were attenuated by co-administration of LY294002. DISCUSSION: GDF15 exacerbates coagulopathy, inflammatory responses, and multiorgan damage in septic rats, likely by activating the PI3K/AKT/mTOR signaling pathway. These results establish GDF15 as a potential mediator of sepsis pathophysiology and a therapeutic target warranting further investigation. CONCLUSION: The findings of this study suggest that GDF15 is associated with coagulation dysfunction, inflammatory responses, and multi-organ injury in septic rats, and these effects may involve modulation of the PI3K/AKT/mTOR signaling pathway. Regarding translational implications, GDF15 has potential as a biomarker, but human validation is required. It may represent a potential therapeutic target that warrants further investigation, and its clinical relevance requires confirmation in human studies. It is important to emphasize that these findings are derived from a preclinical rat model and may not directly translate to human sepsis.
Identification and Validation of Hub Ferroptosis‑Related Genes in Sepsis: An Integrated Bioinformatics and Experimental Study.
Wan F, Ma J
Curr Mol Med · 2026 Jun · PMID 42257259 · Publisher ↗
INTRODUCTION: Sepsis is a life-threatening condition with heterogeneous pathogenesis. This study aimed to identify ferroptosis-related hub genes, construct their regulatory network, and evaluate their potential as biomar...
INTRODUCTION: Sepsis is a life-threatening condition with heterogeneous pathogenesis. This study aimed to identify ferroptosis-related hub genes, construct their regulatory network, and evaluate their potential as biomarkers and therapeutic targets to elucidate the molecular mechanisms underlying sepsis heterogeneity. METHODS: Transcriptomic data from 1,042 sepsis patients and 42 controls were integrated from public databases (GEO and ArrayExpress). Based on the expression of 47 ferroptosis-related genes, consensus clustering was performed to identify molecular subtypes. Differentially Expressed Genes (DEGs) between subtypes were identified and analyzed by functional enrichment. Key gene modules were identified using Weighted Gene Co-Expression Network Analysis (WGCNA), and hub genes were screened by intersecting WGCNA results with a Protein-Protein Interaction (PPI) network. An in silico-predicted multi-factor (TF-miRNA-mRNA) regulatory network was constructed using the starBase and Harmonizome databases. Key findings were preliminarily validated in a mouse model of E. coli-induced sepsis using quantitative real-time PCR (qRT-PCR). RESULTS: Sepsis patients were stratified into two distinct ferroptosis-based subtypes (Cluster 1, n=702; Cluster 2, n=340). A total of 3,608 DEGs were identified, which were enriched in neutrophil activation, ubiquitination, and bacterial infection. WGCNA identified a key sepsis-associated module, leading to the selection of 21 hub genes from the co-expression network. In the septic mouse model, 9 of these genes (including ANK1, HMBS, and SIAH2) were significantly upregulated, and 2 genes (CA1, HBD) were downregulated in septic mice, providing preliminary experimental support for the bioinformatic findings. A comprehensive in silico-predicted regulatory network involving these 21 hub genes, 146 transcription factors, and 70 miRNAs was established as a resource for hypothesis generation. DISCUSSION: The identified hub genes and their regulatory network shed light on the role of ferroptosis in sepsis heterogeneity and pathogenesis. Genes such as SIAH2 and HMBS were differentially expressed between surviving and non-surviving patients, warranting further investigation as potential prognostic biomarkers in future studies. The constructed network identifies actionable targets (e.g., the E3 ligase SIAH2 and specific miRNAs) for therapeutic intervention. Limitations include the retrospective nature of the bioinformatic analysis and the need for further experimental validation of mechanistic roles. CONCLUSION: This study delineates a ferroptosis-associated gene signature and regulatory network in sepsis, providing a hypothesis-generating foundation for future research. The identified hub genes and their regulatory interactions warrant further investigation to explore their potential as prognostic biomarkers or therapeutic targets. However, given the lack of significant association with survival outcomes in the current dataset, these findings should be considered preliminary and require validation in independent cohorts with comprehensive clinical annotation before any clinical applications can be considered.
Screening of Inflammatory Biomarkers in Atherosclerosis Based on WGCNA Analysis and Machine Learning.
Xu X, Jiang M, Huang Z … +1 more , Zhu G
Curr Mol Med · 2026 May · PMID 42227555 · Publisher ↗
INTRODUCTION: Inflammatory response-related signaling pathways are associated with Atherosclerosis (AS), yet the particular inflammation-related genes underpinning this process are still not fully characterized. METHODS:...
INTRODUCTION: Inflammatory response-related signaling pathways are associated with Atherosclerosis (AS), yet the particular inflammation-related genes underpinning this process are still not fully characterized. METHODS: In this study, we integrated two independent transcriptomic datasets with a manually curated inflammation-related gene collection. To identify inflammation-related genes with altered expression, we intersected inflammation-related genes (IRGs), differentially expressed genes (DEGs) between atherosclerosis (AS） and controls, and inflammation score-associated genes (ISRGs) obtained from weighted gene coexpression network analysis (WGCNA) for downstream analyses. The shared genes among these sets were designated as differentially expressed inflammation-related genes (DEIRGs). We then used the DEIRGs to assemble a protein-protein interaction (PPI) network and screen for potential hub genes. Univariate logistic regression, together with least absolute shrinkage and selection operator (LASSO) regression, was used to screen candidate inflammation-related biomarkers. Their expression was then validated by reverse transcription quantitative polymerase chain reaction (RTqPCR). On the basis of the validated biomarkers, we constructed a diagnostic model. As a final analysis, Ingenuity Pathway Analysis (IPA) was used to clarify the major signaling pathways and regulatory networks associated with these biomarkers. RESULTS: Nineteen DEIRGs were obtained as the intersection of the IRG, DEG, and ISRG gene sets. Then, 16 critical genes were identified following PPI analysis. Next, 13 feature genes were filtered using logistic analysis, of which 11 were protective elements, and 2 were risk elements. Four biomarkers (PIK3R5, ADM, RGS16, and B7RP1) were screened by LASSO analysis and RT-qPCR. IPA showed that these inflammation-related biomarkers are mainly enriched in humoral immunity and pathogen-related signaling pathways. Meanwhile, analysis of the regulatory network indicated that STAT3 and KLF6 activated ADM expression and IFNA2 activated IFNAR1 expression. CONCLUSION: In this study, we identified four inflammation-related biomarkers of AS (ADM, PIK3R5, B7RP1 and RGS16) that may serve as novel indicators for the diagnosis of patients with atherosclerosis.
The Mutational Landscape of Angiosarcoma: Challenges and Opportunities to Design Management Strategies.
Pandey SK, Arya S, Mishra A
Curr Mol Med · 2026 May · PMID 42227554 · Publisher ↗
Angiosarcoma is a rare, highly aggressive endothelial malignancy comprising less than 1% of soft tissue sarcomas, with a 5-year overall survival of only 41-43%. Despite advances in cancer therapeutics, angiosarcoma remai...
Angiosarcoma is a rare, highly aggressive endothelial malignancy comprising less than 1% of soft tissue sarcomas, with a 5-year overall survival of only 41-43%. Despite advances in cancer therapeutics, angiosarcoma remains critically understudied due to limited case prevalence, perpetuating a knowledge gap in molecular mechanisms and therapeutic strategies. Recent clinical trials (Axi-STS, TAPPAS) demonstrated that single-agent anti-angiogenic inhibitors (axitinib, pazopanib) achieve modest efficacy (median progression-free survival (PFS) 3.0-4.3 months, response rates 5-13%), underscoring angiosarcoma's complex, multipathway-driven pathogenesis. This review synthesizes the mutational landscape and molecular crosstalk of angiosarcoma, emphasizing four key mechanisms - (1) genepathway interactions-MYC amplification (>95% in radiation-associated angiosarcoma (RAAS)), TP53 mutations, and PIK3CA alterations converging to drive aggressive angiogenesis; (2) endothelial-specific dysregulation-TP53-driven disruption of VEcadherin junctions, VEGF-induced vascular permeability, and endothelial-tomesenchymal transition; (3) microenvironmental contributions- Transforming Growth Factor-Beta (TGF-β), IL-10, and VEGF-mediated immunosuppression and tumor progression; and (4) emerging biomarker-driven combinations-dual Vascular Endothelial Growth Factor (VEGF) + endoglin inhibition, chemotherapy + anti-PD-L1 immunotherapy, and multi-targeted TKI + Immune Checkpoint Inhibitors (ICI) strategies showing improved outcomes. Environmental exposures (vinyl chloride, thorotrast, radiation) drive distinct angiosarcoma subtypes with subtype-specific mutational profiles. We propose that precision-medicine approaches integrating molecular stratification, pathway crosstalk analysis, and biomarker-guided combination therapies represent the rational next steps to overcome therapeutic resistance and improve clinical outcomes in this lethal malignancy.
A Real-world Pharmacovigilance Study of the FAERS Database: Safety Signals of Common Medications for Non-infectious Uveitis.
Zhang X, Wang J, Lu A … +3 more , Li K, Su G, Yang P
Curr Mol Med · 2026 May · PMID 42227553 · Publisher ↗
INTRODUCTION: While a range of immunomodulatory medications are used for non-infectious uveitis (NIU), real-world pharmacovigilance data focusing on their safety profiles are lacking. This study aimed to evaluate the saf...
INTRODUCTION: While a range of immunomodulatory medications are used for non-infectious uveitis (NIU), real-world pharmacovigilance data focusing on their safety profiles are lacking. This study aimed to evaluate the safety of commonly used medications for NIU and provide insights into their associated adverse events (AEs). METHODS: Data on medications used for NIU (from the fourth quarter of 2014 to the second quarter of 2024) were obtained from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) were calculated for AEs signal detection. A significant safety signal was defined only when it was concurrently identified by both algorithms. RESULTS AND DISCUSSION: Among ten medications for NIU, adalimumab accounted for the highest number of AEs reports (N=5,842), followed by infliximab (N=1,199), prednisone (N=749), and methotrexate (N=427). Common AEs were observed in the present study. For instance, AEs of infections (N=293) and endocrine disorders (N=47) were reported in prednisone. We also found several AEs which had not been reported in NIU patients before, with splenomegaly as an example (ROR 95% CI lower bound: 4.66; IC025: 1.35; P<0.001). Moreover, some rare AEs were identified. The disproportionality analysis identified a significant signal for neoplasms associated with biologics (ROR 95% CI lower bound:1.42; IC025: 0.66; P<0.001). This disproportionality analysis provides real-world evidence for a more comprehensive safety spectrum of NIU medications. CONCLUSION: Medications for NIU cause AEs across multiple systems. This study provides valuable insights into the similarities and differences in the safety of NIU medications, including common, novel, and rare AEs. Clinicians should carefully weigh the visual benefits against risks and tailor individual treatment plans for patients with NIU.
Identification of Potential Plasma Biomarkers of Abdominal Aortic Aneurysm Using a Metabolomics Approach.
Wang W, Chen Z, Tang X … +7 more , Wang X, Wu L, Xiang W, Zhang Z, Feng H, Wu J, Zheng Y
Curr Mol Med · 2026 May · PMID 42227552 · Publisher ↗
OBJECTIVE: In the aging population, abdominal aortic aneurysm (AAA) is a widespread and serious disease. Currently, there are no available biomarkers for diagnosing or treating AAA with drugs in clinical use. Uncovering...
OBJECTIVE: In the aging population, abdominal aortic aneurysm (AAA) is a widespread and serious disease. Currently, there are no available biomarkers for diagnosing or treating AAA with drugs in clinical use. Uncovering the metabolic signatures of AAA may provide new insights into its pathogenesis and facilitate the identification of novel metabolic biomarkers. METHODS: In the present study, we applied high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)-based metabolomics to analyze plasma samples from 76 AAA patients and 72 controls. RESULTS: A total of 115 differentially abundant metabolites were identified, and these metabolites were mainly involved in retinol metabolism, glutathione metabolism, purine metabolism, D-amino acid metabolism, pantothenate and CoA biosynthesis, porphyrin metabolism, and sphingolipid metabolism. After biomarker screening in the discovery cohort and biomarker verification in the validation cohort, 28 potential metabolite biomarkers of AAA were identified. Further examination indicated that three metabolites, including 5-Delta-Hydroxybutyl Hydantoin, 2-Amino-4-[(2- hydroxy-1-oxopropyl) amino] butanoic acid, and 15(R),19(R)-hydroxy PGF2, showed remarkable sensitivity and specificity in diagnosing AAA, with AUC values of 0.997, 0.989, and 0.978, respectively. DISCUSSION: This metabolomics study revealed distinct plasma metabolic profiles in AAA patients compared to controls, identifying 115 differentially abundant metabolites. These metabolites were primarily enriched in pathways including retinol metabolism, glutathione metabolism, and purine metabolism. Three metabolites-5-delta-hydroxybutyl hydantoin, 2-amino-4-[(2-hydroxy-1- oxopropyl) amino] butanoic acid, and 15(R),19(R)-hydroxy-PGF2α-were identified as novel potential biomarkers and showed excellent diagnostic performance in combination. The findings suggest that dysregulation of retinol metabolism, implicated in vascular homeostasis, and glutathione metabolism, linked to oxidative stress and ferroptosis, may play roles in AAA pathogenesis. Alterations in purine metabolism further support the involvement of inflammatory and oxidative processes. While these biomarkers show promise, their functional roles in AAA and clinical utility require validation in larger, multicenter prospective studies. CONCLUSION: This study identified potential novel plasma biomarkers of AAA, which could contribute to the discovery of diagnostic biomarkers and therapeutic targets for this disease.
Causal Associations Between Three Types of Anemia and Pulmonary Tuberculosis: A Bidirectional Mendelian Randomization Study.
Liu D, Lai Y, Zhou Y … +1 more , Zhuang W
Curr Mol Med · 2026 May · PMID 42227551 · Publisher ↗
INTRODUCTION: Anemia and pulmonary tuberculosis (PTB) are major global public health problems. Available observational studies have suggested a potential link between them. However, the causal relationship between anemia...
INTRODUCTION: Anemia and pulmonary tuberculosis (PTB) are major global public health problems. Available observational studies have suggested a potential link between them. However, the causal relationship between anemia and PTB remains uncertain. Therefore, our study aims to investigate the causal relationship between different anemia types and PTB by bidirectional Mendelian Randomization (MR) analysis. METHODS: Pernicious Anemia (PA), Iron Deficiency Anemia (IDA), Aplastic Anemia (AA), and PTB genetic summary data were obtained from several independent large Genome-Wide Association Studies (GWAS). The Inverse Variance Weighting (IVW) method was used as the primary method for MR analysis, complemented by methods such as weighted median and MR-Egger to enhance the robustness of the MR analysis. In addition, sensitivity analyses and heterogeneity tests were conducted to assess the robustness of the results and identify potential sources of heterogeneity. RESULTS: Our study showed a causal relationship between PA and PTB (IVW: OR = 1.135, 95% CI = 1.035-1.244, p = 0.007). However, there was no evidence of a causal relationship between IDA and PTB or between AA and PTB. In addition, reversedirection MR analysis found no evidence of causal effects between PTB and these three anemias. DISCUSSION: This study identified a significant positive causal effect of PA on PTB. Therefore, it is recommended to strengthen screening for PTB-related indicators in PA patients in clinical practice. Additionally, in regions with high PTB incidence, PA can be designated as a risk warning indicator for PTB. Vitamin B12 malabsorption, a characteristic feature of PA, may play a crucial role in the causal relationship between PA and PTB. CONCLUSION: Our study is the first to explore the genetic causality between anemia and PTB, identifying PA as a significant genetic risk factor for PTB. Future studies are needed to elucidate the underlying mechanisms and provide new insights into the prevention and treatment of PTB.
Metabolite-Based Biomarkers for Autism Spectrum Disorder: Current Research Progress.
Zhou H, Tang W, Zhang Y … +5 more , Shi W, Ren Y, Dai J, Ghiladi RA, Wang J
Curr Mol Med · 2026 May · PMID 42227550 · Publisher ↗
Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder. Its global prevalence has risen significantly and continuously in recent years, currently affecting approximately 1 in 36 individuals...
Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder. Its global prevalence has risen significantly and continuously in recent years, currently affecting approximately 1 in 36 individuals in the United States, making it a major worldwide public health concern. The etiology of ASD is complex, involving genetic, environmental, and interactive factors. Within this multifactorial framework, dysregulation of metabolic pathways is increasingly recognized as a pivotal driver in ASD pathogenesis. Although previous investigations have primarily focused on metabolite abnormalities within isolated pathways or specific biospecimens (e.g., blood, urine), the collective evidence remains fragmented, lacking a systematic and integrative characterization of metabolic disturbances in ASD. To address this gap, this review aims to systematically synthesize and evaluate metabolic biomarkers associated with ASD. We categorize these biomarkers according to their core pathobiological functions into five interrelated mechanistic domains for detailed discussion: neurotransmitter dysfunction, immune dysregulation, mitochondrial dysfunction, oxidative stress, and gut microbiota dysbiosis. By integrating the current evidence, we not only delineate characteristic metabolite alterations within each domain but also explore the potential cross-talk between these pathways. The identification of candidate biomarkers for early detection and to inform future strategic directions for the development of ASD interventions.
Sappanone A Ameliorates Cisplatin-induced Cytotoxicity Via Nrf2/HO-1 Signaling in HK-2 Cells.
Zheng G, Liu Y, Li B … +2 more , Yang F, Kang L
Curr Mol Med · 2026 May · PMID 42227549 · Publisher ↗
OBJECTIVE: To explore the role of the Nrf2 signaling pathway in sappanone A (SA)-mediated protection against cisplatin (CP)-induced renal injury, we investigated the impact of Nrf2 knockdown on cell apoptosis, oxidative...
OBJECTIVE: To explore the role of the Nrf2 signaling pathway in sappanone A (SA)-mediated protection against cisplatin (CP)-induced renal injury, we investigated the impact of Nrf2 knockdown on cell apoptosis, oxidative stress, NF-κB activation, and IL-1β release in human renal proximal tubular cell line HK-2 cells. MATERIALS AND METHODS: siRNA-mediated knockdown of the Nrf2 gene was performed in HK-2 cells. Oxidative stress markers, including malondialdehyde (MDA) and hydroxyl radical (•OH), were quantified using colorimetric assays. Apoptotic cell death was evaluated by both TUNEL staining and flow cytometry. Western blot analysis was employed to detect protein expression levels of Nrf2, heme oxygenase-1 (HO-1), p65, and phosphorylated p65 (p-p65). The level of interleukin-1β (IL-1β) in cell culture supernatants was measured using ELISA. RESULTS: Down-regulation of Nrf2 significantly suppresses SA's protective effect against CP-induced oxidative stress, as reflected by increased MDA and •OH as well as reduced the expression of HO-1 in HK-2 cells. Nrf2 depletion eliminates SA's capacity to reduce cell apoptosis. SA attenuates CP-induced phosphorylation of NF- κB p65 (p-p65), but this inhibition is reversed by Nrf2 depletion. ELISA analysis further demonstrates that Nrf2 knockdown elevates IL-1β secretion in HK-2 cells, indicating enhanced inflammatory response upon Nrf2 loss. DISCUSSION: SA, an active compound from Caesalpinia sappan L. with antioxidant, anti-inflammatory, and anti-apoptotic properties, mitigates CP-induced nephrotoxicity in HK-2 cells by suppressing oxidative stress, inflammation, and apoptosis through activating the Nrf2 pathway (enhancing Nrf2 and HO-1 expression), as confirmed by experiments showing SA reduces biomarkers of these processes and that Nrf2 silencing abolishes such effects, aligning with classical Nrf2 activation patterns. CONCLUSION: Nrf2-mediated inhibition of oxidative stress, apoptosis, and inflammation contributes to the protective effect of Sappanone A against cisplatininduced cytotoxicity in HK-2 cells.
Plasticity in Cancer Cells: The Master Engine of Therapeutic Resistance and Tumor Evolution.
Ahmad A
Curr Mol Med · 2026 May · PMID 42220158 · Publisher ↗
Cancer cell plasticity refers to the ability of cancer cells to change their phenotype and is one of the primary requirements for metastasis. It is considered one of the main contributors to intratumoral heterogeneity, a...
Cancer cell plasticity refers to the ability of cancer cells to change their phenotype and is one of the primary requirements for metastasis. It is considered one of the main contributors to intratumoral heterogeneity, a key factor in the development of cancer, and is known to alter responses and resistance to different forms of therapy. However, tumour cells are impaired in various cellular signalling pathways, such as mitogen-activated protein kinases, phosphoinositide-3-kinases, Wnt, Hedgehog, and Notch, as well as in epithelial-mesenchymal transition (EMT) and phenotypic plasticity. Cancer stem cells (CSCs) are considered an integral part of tumour plasticity, as they have the capacity to proliferate, differentiate, and initiate the growth of tumours. Recent studies suggest that targeting signals from the tumor microenvironment, plasticity-related pathways, and epigenetic regulators may offer promising therapeutic options to improve long-term response and reduce phenotypic dysregulation. This approach, which emphasizes plasticity as a primary biological driving force rather than a secondary one, allows cancer cells to change from an epithelial, mesenchymal, stem cell, or dormant state to a drug-resistant state in response to environmental stimuli. Taken together, these results suggest that cellular plasticity is important in tumour development and treatment failure. Therefore, targeting pathways associated with plasticity, modifying the tumour microenvironment, and using adaptive therapies may improve long-term tumour control.
Molecular Mechanisms of Cell Death in Multiple Sclerosis: Emerging Targets for Therapeutic Intervention.
Tan RE, Zhang SH, Ling APK … +5 more , Chye SM, Salvamani S, Lim CSY, Subramaiam H, Koh RY
Curr Mol Med · 2026 May · PMID 42163684 · Publisher ↗
Multiple sclerosis (MS) is an autoimmune disease that impacts the brain and spinal cord, which constitute the Central Nervous System (CNS), causing demyelination, inflammation, and neurodegeneration. It is a prevalent di...
Multiple sclerosis (MS) is an autoimmune disease that impacts the brain and spinal cord, which constitute the Central Nervous System (CNS), causing demyelination, inflammation, and neurodegeneration. It is a prevalent disease with limited biomarkers and treatment options. Emerging evidence, primarily from preclinical models like experimental autoimmune encephalomyelitis (EAE) and supported by human tissue studies, has explored the link between MS and various cell death pathways, including apoptosis, autophagy, necroptosis, ferroptosis, and pyroptosis. The involvement of these pathways in MS suggests the potential use of their associated molecules as biomarkers and the intervention in these pathways as therapeutic strategies. This review highlights the double-edged nature of apoptosis and autophagy: their inhibition or stimulation can either reduce or exacerbate MS progression. On the other hand, inhibiting necroptosis, ferroptosis, and pyroptosis may consistently reduce MS progression. More rigorous studies are needed to elucidate the complex relationship among MS, apoptosis, and autophagy. Molecules involved in necroptosis (such as RIPK1, RIPK3, and MLKL), ferroptosis (such as GPX4 and lipid peroxides), and pyroptosis (such as NLRP3, caspase-1, and gasdermin D) show promise as potential biomarkers for MS. Inhibitors targeting these pathways, including necrostatins (for necroptosis), ferrostatins and liproxstatins (for ferroptosis), and NLRP3 inhibitors (for pyroptosis), may offer new approaches for reducing disease progression. A comprehensive strategy that incorporates both reliable biomarkers and targeted treatments would significantly improve MS management in terms of diagnosis, monitoring, and treatment.
Integrated Histopathological and Molecular Classification of Breast Cancer Using Immunohistochemistry (ER, PR, HER2) and KI-67.
Abbas FF, Kamil S, Khan N … +4 more , Shahid R, Kamil N, Ghazi Haider M, Ali R
Curr Mol Med · 2026 May · PMID 42163683 · Publisher ↗
INTRODUCTION: Molecular classification of breast cancer based on Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal growth factor Receptor-2 (HER2) expression has improved therapeutic decision-making...
INTRODUCTION: Molecular classification of breast cancer based on Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal growth factor Receptor-2 (HER2) expression has improved therapeutic decision-making; however, accurate differentiation between luminal subtypes remains challenging. The Ki-67 proliferation index is a valuable biomarker for assessing tumor aggressiveness and guiding treatment strategies. This study aimed to determine the frequency of molecular subtypes in breast cancer biopsies and evaluate their association with clinicopathologic parameters. METHODOLOGY: A cross-sectional study was conducted at the Histopathology Section of the Dow Diagnostic Research and Referral Laboratory (DDRRL), Dow University of Health Sciences (DUHS), Karachi, from January to December 2024. A total of 913 breast cancer biopsy specimens were analyzed using immunohistochemistry for ER, PR, HER2, and Ki-67. Tumors were classified into Luminal A, Luminal B, HER2- enriched, and Triple-Negative Breast Cancer (TNBC). Ethical approval was obtained from the DUHS Institutional Review Board (IRB-3423/DUHS/Approval/2024/93). RESULTS: Among 913 patients, middle-aged adults [41-60 years] were most commonly affected. Luminal A [41%] was the predominant subtype, and invasive ductal carcinoma was the most frequent histological pattern. Molecular subtypes showed significant associations with tumor grade, histology, and laterality, with TNBC exhibiting a higher frequency of Grade III tumors. DISCUSSION: Luminal A tumors were predominantly Grade II and hormone receptor- positive, whereas TNBC demonstrated higher grades and aggressive behavior. An inverse relationship between ER/PR and HER2 expression was observed. High Ki-67 index correlated with higher tumor grade and ER/PR negativity. CONCLUSION: Combined histopathological and molecular classification provides important prognostic information and supports individualized breast cancer management.
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