Current Molecular Medicine[JOURNAL]
Sun
200 papers
Gut Microbiota-Induced Long Non-Coding RNA Snhg9 Regulates the Development of Human Malignant Tumors.
Jia D, He Y, Chen Q … +1 more , Zhang Y
Curr Mol Med · 2025 Jul · PMID 40619655 · Publisher ↗
Gut microbes influence the progression of human malignancies through their recognition by the immune system and their effects on numerous metabolic pathways. Long non-coding RNA is a key target of intestinal microbiota i...
Gut microbes influence the progression of human malignancies through their recognition by the immune system and their effects on numerous metabolic pathways. Long non-coding RNA is a key target of intestinal microbiota involved in the progression of human malignant tumors. Current research shows that there is a close cross-talk between long non-coding RNA Snhg9 and intestinal microorganisms, and it is widely involved in the progression of human malignant tumors. An in-depth study of the interaction between long non-coding RNA and intestinal flora and the intrinsic regulatory mechanism of snhg9 will provide new and powerful therapeutic targets for future research on human malignant tumors.
Pancreatic Elastase Affects Liver Injury by Activating Pro-Inflammatory Cytokines in Kupffer Cells via the JAK2/STAT3 Signaling Pathway.
Feng Y, Jin X, Xu H … +3 more , Sun B, Guo M, Li M
Curr Mol Med · 2025 Jul · PMID 40605170 · Publisher ↗
INTRODUCTION: This study aimed to investigate the role of JAK2 (Janus kinase 2)/STAT3 (signal transducer and activator of transcription 3) signaling in liver injury during severe acute pancreatitis (SAP), focusing on pan...
INTRODUCTION: This study aimed to investigate the role of JAK2 (Janus kinase 2)/STAT3 (signal transducer and activator of transcription 3) signaling in liver injury during severe acute pancreatitis (SAP), focusing on pancreatic elastase- and lipopolysaccharide (LPS)-induced Kupffer cell (KC) activation. METHODS: A rat SAP model was established via retrograde taurocholic acid infusion into the biliopancreatic duct. Inflammatory cytokine levels and JAK2/STAT3 pathway activity were quantified in liver tissues. KCs were treated with elastase/LPS ± AG490 (JAK2 inhibitor). Proinflammatory cytokines, RNA, and protein expression were analyzed. RESULTS AND DISCUSSION: SAP rats exhibited elevated TNF-α, IL-6, and IL-18 levels in both serum and liver tissues, with JAK2/STAT3 pathway activation. AG490 administration suppressed JAK2/STAT3 activation, reduced inflammation, and alleviated liver injury. Similarly, KCs treated with elastase and LPS showed increased proinflammatory cytokine levels and JAK2/STAT3 upregulation, which were mitigated by AG490 treatment. CONCLUSION: The findings highlighted the pivotal role of the JAK2/STAT3 signaling pathway in SAP-induced liver injury. Selective inhibition of this pathway by AG490 could reduce inflammation and protect against liver damage, suggesting its potential as a therapeutic target for inflammatory liver diseases.
Role of Exosomes from Nucleus Pulposus Cells in Attenuating Intervertebral Disc Degeneration by Inhibiting Nucleus Pulposus Cell Apoptosis via the miR-8485/GSK-3β/Wnt/β-catenin Signaling Axis.
Zhang W, Zhang P, Zhan J … +9 more , Wei X, Du Y, Zhao K, Zhu L, Xie R, Xie H, Zhou S, Wang G, Cai C
Curr Mol Med · 2026 · PMID 40600527 · Publisher ↗
BACKGROUND: Studies have shown that abnormal stress is a significant inducer of Intervertebral Disc Degeneration (IVDD). Although traction force is commonly used to delay IVDD, its effects on Nucleus Pulposus Cells (NPCs...
BACKGROUND: Studies have shown that abnormal stress is a significant inducer of Intervertebral Disc Degeneration (IVDD). Although traction force is commonly used to delay IVDD, its effects on Nucleus Pulposus Cells (NPCs) and their secreted exosomes remain unclear. In addition, this study systematically revealed the relationship between miR-8485 and IVDD for the first time. METHODS: Cellular experiments were performed using a Flexcell cell stretching platform to apply traction force to NPCs. After optimizing loading parameters, NPCderived exosomes (NPCs-exo) were isolated and subjected to miRNA high-throughput sequencing. Differentially expressed miRNAs were identified, and their regulatory effects on the Wnt/β-catenin pathway were investigated. Ex vivo rabbit spinal samples were used to validate the cellular experimental results under traction force loading. RESULTS AND DISCUSSION: NPCs-exo were found to be internalized by NPCs, and traction force promoted NPCs-exo secretion. High-throughput sequencing and differential expression analysis identified miR-8485 as a differentially expressed miRNA in NPCs-exo secreted under Cyclic Mechanical Tension (CMT) conditions. Dual-luciferase reporter assays confirmed the targeted regulatory relationship between miR-8485 and GSK-3β, as well as its involvement in the Wnt/β-catenin pathwaymediated regulation of NPCs degeneration. Ex vivo experiments, including morphological and immunofluorescence analyses, revealed that the traction group exhibited better morphology than the pressure group, with a more organized AF, NP, and higher NPCs content, though some loss persisted. Both groups showed significant differences in ECM markers (Collagen II, Aggrecan, MMP3) compared to the control (p < 0.05). Additionally, the traction group had significantly higher Collagen II and Aggrecan levels than the pressure group (p < 0.05). CONCLUSION: CMT can promote the secretion of NPCs-exo, which are internalized by the NPCs. Through the delivery of miR-8485, NPCs-exo target and regulate GSK-3β, thereby enhancing Wnt/β-catenin pathway activity. This mechanism increases NPCs viability and extracellular matrix synthesis while suppressing apoptosis, ultimately delaying IVDD progression. Immunofluorescence staining in animal experiments confirmed that traction force effectively improves extracellular matrix expression in the IVD and mitigates stress-induced morphological alterations of the IVD.
The Role of the TRIM Family in Lung Cancer Development: An Emerging Player with Therapeutic Potential.
Li J, Wang Y, Huang J … +4 more , Wang W, Cheng D, Yang Q, Peng X
Curr Mol Med · 2026 · PMID 40574398 · Publisher ↗
Lung cancer is one of the most prevalent malignancies and a leading cause of cancer-related deaths worldwide. E3 ubiquitin ligase activity is a common feature of most TRIM proteins, highlighting the family's critical rol...
Lung cancer is one of the most prevalent malignancies and a leading cause of cancer-related deaths worldwide. E3 ubiquitin ligase activity is a common feature of most TRIM proteins, highlighting the family's critical role in regulating the biological behaviors of tumor cells and influencing various cellular physiological activities, including apoptosis, innate immunity, development, and intracellular signaling. In lung cancer, certain TRIM proteins function either as oncoproteins or cancer suppressors. This review explores the unique function of TRIM in lung cancer development, focusing on the molecular processes of TRIM proteins. Finally, we provide an overview of recent advancements in the prognosis and therapeutic strategies for lung cancer involving TRIM proteins.
Exploring the Therapeutic Role of Pregnane X Receptor Activation in Acute Kidney Injury: Mechanisms and Clinical Implications.
Fan Q, Song H, Zhang K … +6 more , Kan C, Sheng S, Ma Y, Sun X, Pan R, Guo Z
Curr Mol Med · 2025 Jun · PMID 40511830 · Publisher ↗
Acute Kidney Injury (AKI) is a critical condition characterized by a rapid decline in kidney function, often resulting from ischemia-reperfusion, nephrotoxicity, or inflammation. Current treatments primarily rely on rena...
Acute Kidney Injury (AKI) is a critical condition characterized by a rapid decline in kidney function, often resulting from ischemia-reperfusion, nephrotoxicity, or inflammation. Current treatments primarily rely on renal replacement therapies, which remain limited and controversial. The pregnane X receptor (PXR), a nuclear receptor involved in drug metabolism, immune regulation, and cellular homeostasis, has emerged as a promising target for AKI therapy. Preclinical studies suggest that PXR activation demonstrates protective effects in AKI through multiple mechanisms, including reducing inflammation, oxidative stress, and mitochondrial dysfunction. Specifically, PXR modulates nuclear factor-κB (NF-κB) signaling, supports mitochondrial function, regulates apoptosis, and enhances renal hemodynamics, thus mitigating AKI progression. Furthermore, PXR's role in the gut-liver-kidney axis strengthens intestinal barrier integrity and bile acid homeostasis, contributing to renal protection. Recent advances in research on the PXR agonists rifampicin and tanshinone IIA (TanIIA) highlight the potential of PXR-targeted therapies to mitigate nephrotoxicity and promote kidney recovery. This review provides a comprehensive analysis of PXR's protective mechanisms in AKI, underscoring its therapeutic potential and paving the way for new treatment strategies.
HUPO 2024 CONFERENCE REPORT.
Guttman A
Curr Mol Med · 2025 · PMID 40495609 · Publisher ↗
Abstract loading — click title to view on PubMed.
Hemochromatosis and Hepatic Complications: A Comprehensive Review of Molecular Mechanisms, Diagnostics, and Emerging Therapeutics.
Ikhtiar F, Jamal A, Arif A … +2 more , Shahid MN, Bokhari SMSM
Curr Mol Med · 2025 Jun · PMID 40468930 · Publisher ↗
Hemochromatosis is an autosomal recessive iron overload disorder. It occurs due to a failure in the hepcidin response, leading to systemic iron overload. The high iron levels in the plasma stored in various organs cause...
Hemochromatosis is an autosomal recessive iron overload disorder. It occurs due to a failure in the hepcidin response, leading to systemic iron overload. The high iron levels in the plasma stored in various organs cause injury and permanent damage. There are two types of hemochromatosis: primary and secondary. In non- HFE hemochromatosis, mutations in the HJV, HAMP, TRF2, and SLC40A1 genes are implicated, with the associated condition classified as type I hemochromatosis. In contrast, juvenile hemochromatosis (type II hemochromatosis/ HFE II) is linked to mutations in the hemojuvelin gene or the antimicrobial peptide hepcidin. In this study, relevant literature in databases, including PubMed, MEDLINE records, Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar, and Embase, was searched. Our study inclusion criteria encompassed both experimental and observational studies or a combination of both, with data derived from the human population. The exclusion criteria included animal models, observational studies, and unpublished data. Hepcidin is usually up-regulated in response to high serum iron, but it is unexpectedly low in patients with hemochromatosis because of mutations in HFE, hemojuvelin (JH), and transferrin receptor 2 (TfR2). TfR2, expressed by hepatocytes, is mutated in hemochromatosis type III. Future research directions include exploring the molecular mechanisms underlying the effects of the TFR2 gene variant on iron homeostasis and liver damage and investigating potential therapeutic targets for treating hemochromatosis-related liver disease. Additionally, further epidemiological and modern genetic engineering studies are needed to better understand the prevalence and impact of hemochromatosis on liver health in different populations.
Metabolomic Profiling of Leukemic Hematopoiesis: Effects of BNT162b2 mRNA COVID-19 Vaccine Administration.
Erdogdu B, Kaplan O, Fidan BB … +3 more , Celebier M, Malkan UY, Haznedaroglu IC
Curr Mol Med · 2026 · PMID 40464175 · Publisher ↗
BACKGROUND: Leukemia is marked by clonal hematopoietic stem cell expansion and metabolic reprogramming. The BNT162b2 mRNA COVID-19 vaccine has been proven effective, though questions remain about its broader physiologica...
BACKGROUND: Leukemia is marked by clonal hematopoietic stem cell expansion and metabolic reprogramming. The BNT162b2 mRNA COVID-19 vaccine has been proven effective, though questions remain about its broader physiological effects. This study investigates metabolomic alterations in leukemic bone marrow potentially associated with BNT162b2 vaccination. OBJECTIVE: To compare the bone marrow metabolomic profiles of leukemia patients with and without BNT162b2 vaccination, and healthy unvaccinated controls, to explore potential metabolic differences. METHODS: Bone marrow samples were obtained from three groups: vaccinated leukemia patients (n=7), unvaccinated leukemia patients without COVID-19 history (n=2), and unvaccinated healthy controls (n=7). Untargeted metabolomics was performed using LC-QTOF-MS. Data were analyzed using XCMS and MetaboAnalyst 5.0 to identify statistically significant metabolite differences and affected pathways. Fold change >1.5 and p<0.05 were considered significant. RESULTS AND DISCUSSION: Distinct metabolic profiles were observed between the leukemia and control groups. Increased glycolysis, pentose phosphate pathway activity, and altered tryptophan, lipid, and heme metabolism were noted in leukemia samples. Metabolic changes in vaccinated patients (ASL) were more similar to unvaccinated leukemia patients (LO) than to healthy controls, with minor vaccineassociated variations. Notable metabolites included 5-methoxyindoleacetate, phosphorylcholine, and tetrahydrofolic acid. CONCLUSION: This preliminary study identified altered metabolic pathways in leukemia bone marrow and suggests metabolomic differences associated with BNT162b2 vaccination. While the findings do not support a causal link between mRNA vaccination and leukemia development, they highlight the need for further studies to understand vaccine-induced metabolic modulation in hematological contexts.
Oxidized HDL as a Novel Predictive Biomarker in Conjunction with Selected Inflammatory Variables in Severe Dengue Fever Patients from Lahore, Pakistan.
Sarwar M, Kamil N, Ashraf R … +6 more , Ali R, Majeed R, Arif S, Sohail HB, Khan Z, Rehan M
Curr Mol Med · 2025 · PMID 40464174 · Publisher ↗
BACKGROUND: Dengue fever is a deadly disease and represents one of the biggest threats to global health, with persisting uncertainty surrounding its prognosis and treatment standards. The onset of severe dengue fever, ch...
BACKGROUND: Dengue fever is a deadly disease and represents one of the biggest threats to global health, with persisting uncertainty surrounding its prognosis and treatment standards. The onset of severe dengue fever, characterized by intense inflammation and the production of pro-inflammatory molecules, is currently the only well-established association with disease severity. Therefore, identifying and assessing both new and established biomarkers that can accurately predict the outcome of severe dengue fever is essential. METHODS: In this study, 100 age-matched healthy controls and 100 hospitalized dengue patients positive for NS1 and IgM, with a mean age of 45 years (range: 22- 65), were examined. Potential biomarkers were analyzed using a Coulter counter, spectroscopy, and ELISA to determine their prognostic value in assessing dengue fever severity. RESULTS: Triglycerides and very-low-density lipoproteins (VLDL) were significantly higher in severe dengue fever patients compared to controls (p<0.001). Conversely, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and cholesterol levels were significantly lower in patients compared to controls (p<0.001). Albumin levels were 40.9% lower, lactate dehydrogenase (LDH) was 422.1% higher, and C-reactive protein (CRP) levels were 435.6% higher in severe dengue fever patients compared to controls. Unlike HDL, oxidized HDL (oxHDL) levels were 160.4% higher in patients with severe dengue fever compared to controls. Still, the absolute levels of oxHDL did not exceed total HDL levels, as confirmed by corrected data. CONCLUSION: Oxidized HDL, combined with other lipoproteins, may provide an ideal panel of prognostic indicators that could guide the treatment of severe dengue fever and serve as reliable biomarkers for predicting disease outcomes.
Association Between Blood Lead Levels and Diabetic Kidney Disease: A Cross-sectional Analysis of NHANES Data (1999-2018).
Ning Y, Wang J, Zhou X … +2 more , Wang G, Zhang L
Curr Mol Med · 2025 May · PMID 40454506 · Publisher ↗
BACKGROUND: The relationship between heavy metals, particularly lead (Pb), and diabetic kidney disease (DKD) remains unclear, especially regarding exposure thresholds. This study investigates the association between bloo...
BACKGROUND: The relationship between heavy metals, particularly lead (Pb), and diabetic kidney disease (DKD) remains unclear, especially regarding exposure thresholds. This study investigates the association between blood Pb levels and DKD risk using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. METHODS: A total of 1,343 participants were included, with 508 diagnosed with DKD. Baseline characteristics were compared between DKD and non-DKD groups. Multivariate generalized linear models (GLMs) and weighted logistic regression were used to assess correlations between blood Pb levels and DKD risk. A nomogram was developed to evaluate the predictive power of significant clinical characteristics. RESULTS: Key clinical characteristics, including age, marital status, and serum Pb levels, differed significantly between DKD and non-DKD groups. Serum Pb was identified as a significant risk factor (ORs: 1.18-1.39, p < 0.01). The nomogram demonstrated good predictive accuracy (AUC = 0.717). CONCLUSION: Elevated blood Pb levels are significantly associated with DKD, with a non-linear relationship and a defined threshold. These findings highlight the potential role of Pb exposure in DKD pathogenesis and suggest the utility of blood Pb monitoring in diabetic patients.
Urinary CFHR2 as a Biomarker for Early Diagnosis and Disease Progression Prediction in Diabetic Kidney Disease.
Du T, Zhang Q
Curr Mol Med · 2025 May · PMID 40442911 · Publisher ↗
AIM: The pathogenesis of diabetic kidney disease (DKD) is complex, and the specific biomarkers for detecting early diagnosis and monitoring kidney function deterioration are insufficient, which affects the prognosis of p...
AIM: The pathogenesis of diabetic kidney disease (DKD) is complex, and the specific biomarkers for detecting early diagnosis and monitoring kidney function deterioration are insufficient, which affects the prognosis of patients. The complement activation in glomeruli and renal interstitium contributes to the aggravation of DKD. Several key complement proteins, such as complement factor 3 (C3), CD59, and complement factor H-related protein 2 (CFHR2) were reported to be potential biomarkers for early diagnosis and prognosis for DKD. METHODS: In the current study, we focus on CFHR2, to investigate its capability and sensitivity as a DKD biomarker. As a non-invasive detection sample, urine has the characteristic of convenient sampling. In the current study, the urine samples were collected from three groups: diabetic patients without albuminuria, with microalbuminuria, and macroalbuminuria, to analyze whether CFHR2 was associated with albuminuria concentration and declined renal function. Meanwhile, the urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and C3 were also examined by enzyme-linked immunosorbent assay (ELISA) to compare with CFHR2 to determine whether CFHR2 had an advantage in predicting the early detection and progression of DKD. The Spearman correlation analysis was performed for the correlation analysis. The receiver operating characteristic curve was used to analyze the diagnostic efficacy. RESULTS: CFHR2 had superior diagnostic power to predict the early occurrence of DKD and disease progression, compared with NGAL, microalbumin, and C3 in urine. CONCLUSION: CFHR2 has satisfactory potential to be a biomarker for early diagnosis and risk of progression of DKD.
SMAC/DIABLO: A Guardian Angel in Boosting Anticancer Drug-Induced Apoptosis.
Mishra A, Pandey SK
Curr Mol Med · 2025 May · PMID 40396320 · Publisher ↗
Apoptosis is an established hallmark of cancer. In normal conditions, apoptosis is strictly controlled; however, when it is not properly managed, it causes several complications, including cancer progression and drug res...
Apoptosis is an established hallmark of cancer. In normal conditions, apoptosis is strictly controlled; however, when it is not properly managed, it causes several complications, including cancer progression and drug resistance. SMAC/ Diablo (SMAC) is a mitochondrial protein that is released into the cytosol upon activation of BAX/BAK channels with apoptotic signals. SMAC protein interacts and neutralizes inhibitors of apoptosis (IAP) proteins and initiates the caspase cascade, which leads to apoptosis. SMAC is downregulated in several types of cancer, which led to the design of small-molecule inhibitors known as SMAC mimetics as new cancer therapeutics, and some of these molecules are in the clinical phase. It has also been shown that a combination of SMAC with standard anti-cancer drugs could be beneficial to drug-resistant cancer. Despite being a pro-apoptotic protein, it has been found that SMAC/Diablo is overexpressed in several types of cancers like lung, breast, bladder, cervix, pancreas, prostate, and colon, as well as in melanoma and glioma, and in cancer cells. Recently, we have reported that the overexpression of SMAC in cancers is essential for cell and tumor growth due to non-apoptotic regulation of phospholipid synthesis. The current review is focused on apoptotic and non-apoptotic functions of SMAC and its role in drug resistance.
CD82 Methylation Patterns in Inflammatory Arthritis and their Clinical Association with Hypertension in Rheumatoid Arthritis.
Shi Y, Hu H, Zhou M … +10 more , Chang C, Zhao J, Shan Y, Zheng Y, Zhao F, Li Y, Guo S, Fan X, Ma W, He D
Curr Mol Med · 2025 May · PMID 40396297 · Publisher ↗
OBJECTIVE: This study aimed to compare CD82 methylation patterns in peripheral blood among patients with rheumatoid arthritis [RA], inflammatory arthritis, and healthy controls [HC] and to assess their clinical associati...
OBJECTIVE: This study aimed to compare CD82 methylation patterns in peripheral blood among patients with rheumatoid arthritis [RA], inflammatory arthritis, and healthy controls [HC] and to assess their clinical associations with hypertension in RA. METHODS: In this cross-sectional study, CD82 methylation at positions 44596705- 44596865 on chromosome 11 was analyzed using targeted methylation techniques in peripheral blood from patients with RA, psoriatic arthritis [PsA], ankylosing spondylitis [AS], gout, and HC. RESULTS: CD82 cg22143324 methylation levels were significantly different between RA patients and healthy controls [P<0.0001], PsA [P=0.0281], and AS [P=0.0360]. In RA subgroups, individuals negative for both rheumatoid factor [RF] and cyclic citrullinated peptide [CCP] [RA-DN], as well as those positive for both [RA-DP], exhibited significantly different methylation levels compared to HC [P=0.0355 and P<0.0001, respectively]. ROC analysis indicated a promising diagnostic potential for CD82 cg22143324 methylation, especially with the TTT haplotype. Correlation analysis revealed significant associations between CD82 methylation and CCP levels, as well as hypertension in RA patients. CONCLUSION: The analysis conducted revealed altered CD82 cg22143324 methylation in RA, with potential utility in distinguishing seronegative patients from healthy controls. An association between lower methylation levels and comorbid hypertension in RA patients was also observed, warranting further investigation.
miRNA-29b-3p: An Important Target for Ameliorating Liver Fibrosis in Wilson Disease by Inhibiting Autophagy.
Huang P, Huang Y, Dong T … +5 more , Yang Y, He W, Wang M, Wang H, Yang W
Curr Mol Med · 2026 · PMID 40375700 · Publisher ↗
BACKGROUND: Liver fibrosis is an important pathological feature of Wilson disease (WD). The miRNA-29b-3p level decreased in liver fibrosis, while the mechanism of miRNA-29b-3p in liver fibrosis has not been reported, and...
BACKGROUND: Liver fibrosis is an important pathological feature of Wilson disease (WD). The miRNA-29b-3p level decreased in liver fibrosis, while the mechanism of miRNA-29b-3p in liver fibrosis has not been reported, and was elucidated in the work. METHODS: The miRNA-29b-3p levels were evaluated by q-PCR. The effect of miRNA- 29b-3p on the activity of hepatic stellate cells was detected by cell activity assay. The protein levels were checked by western blot. The interaction between miRNA-29b-3p and ULK1 mRNA with base complementary sequences was detected by double luciferase assay. The autophagosomes were observed by TEM. The cell fibrosis-like change was evaluated with an anti-α-smooth muscle actin (α-SMA) antibody by IF. RESULTS AND DISCUSSION: The results showed that miRNA-29b-3p mimics downregulated the α-SMA and Col1 protein levels, and miRNA-29b-3p inhibitors upregulated the α-SMA and Col1 protein levels. The dual-luciferase assay result revealed that miRNA-29b-3p interacted with ULK1. The miRNA-29b-3p mimics inhibited the protein expression of ULK1, beclin1, and LC3, whereas miRNA-29b-3p inhibitors promoted the protein expression of ULK1, beclin1, and LC3. CONCLUSION: The miRNA-29b-3p blocked HSCs trans-differentiation into myofibroblasts by inhibiting autophagy, and further inhibiting liver fibrosis in WD.
Boosting Antiviral Defenses: stat3 Inhibition Enhances Type I Interferon Response to Respiratory Syncytial Virus by Silencing KAP1.
Chen H, Ding D, Teng Z … +1 more , Zhang R
Curr Mol Med · 2025 May · PMID 40370235 · Publisher ↗
INTRODUCTION: The antiviral effects of type I interferons [IFNs] on respiratory syncytial virus [RSV]-infected airway epithelial cells have been identified. We aim to further reveal the mechanism of stat3 and kruppel-ass...
INTRODUCTION: The antiviral effects of type I interferons [IFNs] on respiratory syncytial virus [RSV]-infected airway epithelial cells have been identified. We aim to further reveal the mechanism of stat3 and kruppel-associated box-associated protein 1 [KAP1] in RSV-infected airway epithelial cells. METHODS: Using the A549 cell line, we investigated the impact of RSV infection, KAP1 overexpression, and stat3 inhibition with Stattic. Cell counting kit 8 assay was used to determine the viability, and enzyme-linked immunosorbent assay was applied to measure the levels of IL-6, IL-8, IL-1β, IFN-α, and IFN-β. Viral replication was tested via plaque assay. Meanwhile, quantitative real-time reverse transcription polymerase chain reaction or/and western blot were applied to measure the expressions of p-stat3 and KAP1 in the cells. RESULTS: RSV infection repressed the viability, upregulated p-stat3 and KAP1 expressions, elevated levels of inflammation-related factors [IL-6, IL-8, IL-1β], and type I IFN immune response-associated factors [IFN-α, IFN-β], and promoted viral replication in A549 cells. Stattic attenuated the promoting effect of RSV on inflammation-related factors and viral replication, but enhanced its impact on IFN-α and IFN-β levels in the cells. More importantly, KAP1 overexpression reversed the effects of Stattic on viability, inflammation [IL-6, IL-8, IL-1β], type I IFN immune response [IFN-α, IFN-β], and viral replication in RSV-infected A549 cells. CONCLUSION: Our findings unveil the pivotal role of stat3 inhibition in potentiating type I IFN-mediated antiviral responses against RSV in lung epithelial cells, revealing KAP1 as a potential therapeutic target for combating respiratory viral infections.
Neuroprotective Potential of Conditioned Medium from Adipose and Liver Mesenchymal Stem Cells in a Rat Model of Global Cerebral Ischemia-reperfusion Injury.
Shooshtari MK, Vastegani SM, Farbood Y … +5 more , Sarkaki A, Bayati V, Nejaddehbashi F, Khoshnam SE, Farzaneh M
Curr Mol Med · 2026 · PMID 40357793 · Publisher ↗
BACKGROUND: Mesenchymal stem cell-derived conditioned medium (MSCCM) contains bioactive factors that provide neuroprotection in cases of cerebral ischemia-reperfusion (IR) injury. This study aimed to compare the therapeu...
BACKGROUND: Mesenchymal stem cell-derived conditioned medium (MSCCM) contains bioactive factors that provide neuroprotection in cases of cerebral ischemia-reperfusion (IR) injury. This study aimed to compare the therapeutic potential of rat adipose-derived MSC-CM (rAD-MSC-CM) and chicken embryo liver-derived MSC-CM (cLD-MSC-CM) following global cerebral IR injury in male rats. MATERIAL AND METHODS: We harvested rAD-MSC-CM from the adipose tissue surrounding the epididymis of Wistar rats and cLD-MSC-CM from the liver tissue of 10- day-old chicken embryos. To induce global cerebral ischemia, we utilized a four-vessel occlusion (4VO) model in rats. After inducing ischemia, the conditioned media were administered via intravenous injection 30 minutes post-reperfusion. We evaluated the cognitive and non-cognitive functions of the animals using standard behavioral tests. Additionally, we assessed blood-brain barrier (BBB) permeability, brain water content (BWC), oxidative-antioxidative status, and conducted histopathological analyses of the hippocampal tissue in the IR rats. RESULTS AND DISCUSSION: Our findings demonstrated that treatment with both rADMSC- CM and cLD-MSC-CM significantly improved memory function, reduced anxietyand depression-like behaviors, and enhanced exploratory activities. These behavioral improvements correlated with decreased BBB permeability and BWC, reduced oxidative stress, and mitigated histopathological changes in the hippocampal tissue. CONCLUSION: Our findings suggest that both rAD-MSC-CM and cLD-MSC-CM offer protective benefits against IR injury, likely owing to their antioxidant properties.
MicroRNA-9-5p Alleviates Oxidative Stress, Inflammation, and Apoptosis in Cerebral Ischemia-reperfusion Injury by Targeting NOX4 .
Huang Y, Hou X, Wang Y … +4 more , Cao Y, Zhou Y, Chen Y, Cheng H
Curr Mol Med · 2026 · PMID 40337970 · Publisher ↗
BACKGROUND: Prior research has displayed that the dysregulation of miR- 9-5p is related to cerebral ischemia-reperfusion (I/R) injury. However, the underlying neuroprotective mechanism of miR-9-5p in cerebral I/R injury...
BACKGROUND: Prior research has displayed that the dysregulation of miR- 9-5p is related to cerebral ischemia-reperfusion (I/R) injury. However, the underlying neuroprotective mechanism of miR-9-5p in cerebral I/R injury has not been clarified. MATERIALS AND METHODS: The cerebral I/R injury was simulated by oxygen-glucose deprivation/reperfusion (OGD/R) model that was constructed in human SH-SY5Y cells. Changes in reactive oxygen species (ROS) and superoxide dismutase (SOD) levels were detected with the commercial kits. ELISA assay was applied for measuring the expressions of inflammatory cytokines. Western blot was used for testing the protein levels. Cell apoptosis was measured by TUNEL assay. RESULTS AND DISCUSSION: MiR-9-5p expression was dramatically decreased, while NADPH oxidase 4 (NOX4) expression was significantly increased in SH-SY5Y cells under OGD/R operation. MiR-9-5p over-expression dramatically inhibited OGD/Rinduced oxidative stress, inflammation, and apoptosis in SH-SY5Y cells. Mechanistically, results from luciferase reporter assay demonstrated that NOX4 was a target of miR-9-5p, and NOX4 over-expression partially reversed the effects of miR-9-5p mimic on oxidative stress, inflammation, and apoptosis in OGD/R SHSY5Y cells. CONCLUSION: MiR-9-5p over-expression suppressed oxidative stress, inflammation, and apoptosis in cerebral I/R injury by targeting NOX4, suggesting that miR-9-5p might be a new anti-inflammatory and anti-oxidative modulator in cerebral I/R injury.
Non-coding RNAs PROX1-AS1 and miR-647: Potential Interaction and Prognostic Value in Gastric Cancer.
Bure IV, Vetchinkina EA, Kuznetsova EB … +7 more , Kalinkin AI, Molchanov AD, Kiseleva AE, Alekseeva EA, Gorokhovets NV, Rodionov IV, Nemtsova MV
Curr Mol Med · 2025 May · PMID 40326038 · Publisher ↗
BACKGROUND: Gastric cancer (GC) remains one of the most common malignancies and the third cause of cancer-related deaths worldwide. Non-coding RNAs (ncRNAs), including microRNAs and long ncRNAs, can contribute to the pat...
BACKGROUND: Gastric cancer (GC) remains one of the most common malignancies and the third cause of cancer-related deaths worldwide. Non-coding RNAs (ncRNAs), including microRNAs and long ncRNAs, can contribute to the pathogenesis and progression of GC and therefore could be its potent diagnostic and prognostic biomarkers. The aim of our work was to estimate the expression of PROX1- AS1 (Prospero Homeobox 1 Antisense RNA 1) and miR-647 (microRNA-647) in GC and investigate their potential interaction and clinical significance. METHODS: The study included tumor and adjacent non-tumor tissues from 110 GC patients and plasma samples from 65 GC patients; 38 sectional normal gastric tissue samples and 49 plasma samples of healthy donors were included as controls. Expression levels of both ncRNAs were quantified in all samples by using real-time polymerase chain reaction (RT-PCR) and their possible correlations with the clinical and pathological characteristics of patients were analyzed. A potential inverse correlation between PROХ1-AS1 and miR-647 expression was addressed by in vitro experiments in a panel of cancer cell lines. RESULTS: The expression of PROX1-AS1 and miR-647 was not significantly different in tissues of GC patients and sectional normal gastric tissue samples. However, they have demonstrated a negative correlation both in the tumor and the adjacent nontumor tissue of GC patients. PROX1-AS1 expression was significantly decreased in GC tissues, whereas the miR-647 expression was increased. The expression of the ncRNAs was associated with clinical and pathological characteristics of GC patients. The overexpression of miR-647 led to a significant decrease in PROX1-AS1 expression in five cancer cell lines, including the GC cell line SNU-1. CONCLUSION: We have demonstrated a negative correlation between PROX1-AS1 and miR-647 in both GC tissues and the cancer cell lines. In addition, expression of both ncRNAs was associated with the primary tumor size. Therefore, these ncRNAs might have potential prognostic value.
Innovative Therapeutic Potential of Herbal Extracts Containing Punicic and Ellagic Acid: Addressing Lower Urinary Tract Disorders.
Purkayastha HD, Bhattacharjee A, Swain RP
Curr Mol Med · 2025 · PMID 40325813 · Publisher ↗
This review highlights the new healing frontiers opened by herbal preparations rich in punicic acid, as well as ellagic acid, in the management of Lower Urinary Tract Disorders (LUTD). New data prove that these bioactive...
This review highlights the new healing frontiers opened by herbal preparations rich in punicic acid, as well as ellagic acid, in the management of Lower Urinary Tract Disorders (LUTD). New data prove that these bioactive compounds possess strong anti-inflammatory, antioxidant, and antibacterial properties, and therefore, can be helpful in treating LUTD symptoms such as urgency, frequency, and dysuria. We conducted a comprehensive pharmacological assessment of punicic and ellagic acids aimed at determining their role in bladder health through modulation of inflammatory processes and both alteration and maintenance of urothelium integrity, in addition to obtaining some background information and chemical properties of these acids. Furthermore, we evaluated the findings of clinical and preclinical studies that demonstrated the ability of these formulations to improve the basic functions of the organs in the urinary system and the quality of life of patients. The review also reflects on the use of herbal extracts in combination with current therapies as a synergistic approach, particularly on the healing effects of such combinations and the need for solid clinical evidence to support such claims. This paper focuses on the concept of how LUTDs can be treated safely and effectively without the help of drugs by integrating modern scientific strategies with traditional approaches, which will thus increase the comprehensiveness of treatment in urological care. Future research should focus on improving how well these compounds are absorbed in the body and gathering long-term safety data, with the goal of incorporating them into treatment guidelines.
Immunohistochemical Analysis of CYP11B2 (Aldosterone Synthase) and Evaluation of the HISTALDO Classification in Patients with Primary Aldosteronism.
Karadepe M, Yanar H, Binokay H … +2 more , Erdogan S, Akkus G
Curr Mol Med · 2025 · PMID 40325812 · Publisher ↗
OBJECTIVE: Primary Aldosteronism (PA) is the most common cause of secondary hypertension. Immunohistochemical analysis of PA is based on specific monoclonal antibodies targeting CYP11B1 and CYP11B2, which are enzymes res...
OBJECTIVE: Primary Aldosteronism (PA) is the most common cause of secondary hypertension. Immunohistochemical analysis of PA is based on specific monoclonal antibodies targeting CYP11B1 and CYP11B2, which are enzymes responsible for the aldosterone production in the adrenal cortex. The recently proposed HISTALDO classification introduced CYP11B2 immunohistochemistry to define clinically relevant diagnostic categories. We aimed to investigate the relationship between clinical characteristics and immunohistochemistry of CYP11B2 in PA and also evaluate staining in cortisol-producing cells by comparing patients with Cushing's Syndrome (CS). Consecutive patients diagnosed with PA (n=21) and CS (n=20) were included between 2015-2022. All of them underwent unilateral adrenalectomy in our tertiary center. METHODS: Following hematoxylin and eosin (H&E) staining of the pathological specimens, all slides were re-evaluated and immunostained for CYP11B2. A semiquantitative H-score was assessed for each patient and compared with staining intensity. Patients with PA were grouped and classified according to the HISTALDO classification. RESULTS: The mean size of adenoma in patients with PA was much smaller compared to patients with CS (p=0.001). An increase in the immunohistochemical H-score of the patients with PA (121.36 ±81.04 vs 73.94±57.70, p=0.045) was observed in comparison to the patients with CS. When comparing the patients with PA according to HISTALDO criteria, the H-score of the patients with Aldosterone Producing Adenoma (APA, n=10) was 136.6±78.86 compared to the non-APA group, which was 86.81±85.3 (n=11, p=0.05). Moreover, mean preoperative aldosterone levels (p=0.06) and aldosterone-to-renin ratio (ARR, p=0.03) were higher in patients with APA compared to non-APA patients. Response to surgical therapy was more favorable in patients with APA than the patients with non-APA. CONCLUSION: CYP11B2 is a key enzyme responsible for the synthesis of aldosterone. CYP11B2 expression, as assessed by immunostaining, was associated with the clinical characteristics, severity of PA, and response to the treatment. Hence, immunohistochemical analysis of CYP11B2 should be incorporated into the routine clinical workup to better localize aldosterone-producing cells.
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