Mol. Cell. Biochem. [JOURNAL]
Sun
200 papers
Molecular and immune profiling of colorectal polyps using FTIR microspectroscopy.
Vazquez-Zapien GJ, Martinez-Cuazitl A, Garibay-Gonzalez F … +5 more , Cerda-Reyes E, Lopez-Barrera KM, Garcia-Hernandez JS, Guerrero-Ruiz M, Mata-Miranda MM
Mol Cell Biochem · 2026 Jun · PMID 42048029 · Publisher ↗
Colorectal polyps (CRP) are abnormal protuberances of tissue that grow into the lumen from the typically flat colonic mucosa; according to their morphology, they are classified as sessile or pedunculated, and considering...
Colorectal polyps (CRP) are abnormal protuberances of tissue that grow into the lumen from the typically flat colonic mucosa; according to their morphology, they are classified as sessile or pedunculated, and considering their behaviour, they can be classified as benign or malignant. Some CRP can be precursors to colorectal cancer. Therefore, this research aimed to analyze, using micro-FTIR, the biomolecular components and immune responses in mice with CRP. Fifteen mice of the C57BL/6 strain were randomly divided into two groups: healthy and CRP groups. The murine model of CRP was induced with azoxymethane and dextran sulfate sodium for 50 days. The weight and evaluation of the mouse Grimace scale were evaluated, and morphometric, histopathological, and micro-FTIR analyses of the colon were conducted. Finally, the molecular and immunological profiles were analyzed using micro-FTIR spectra. The CRP group showed weight loss and a significantly higher Grimace scale score than the healthy group. Furthermore, the colon length and weight decreased in the CRP group. Histopathologically, at 40X, a significant number of lymphatic nodules and inflammatory infiltrate were observed. At 100X, dysplasia of the Lieberkühn crypts with a star-shaped appearance was evidenced in the CRP group. In micro-FTIR spectra of the CRP group, the fingerprint region showed lower absorbance, and humoral immunity and cellular responses showed lower expression. The results are consistent with dysplasia features, and spectroscopy suggests that the CRP exhibits immune characteristics of a cold tumor.
Fenofibrate mitigates microglial activation by reprogramming lipid metabolism and inhibiting ferroptosis.
Taskesen A, Hacioglu C, Tuncer S … +2 more , Kilic G, Tuncer C
Mol Cell Biochem · 2026 Jun · PMID 42048028 · Full text
Microglial activation is a central mediator of neuroinflammatory and neurodegenerative processes. Growing evidence indicates that dysregulated lipid metabolism and ferroptosis drive microglial dysfunction, yet pharmacolo...
Microglial activation is a central mediator of neuroinflammatory and neurodegenerative processes. Growing evidence indicates that dysregulated lipid metabolism and ferroptosis drive microglial dysfunction, yet pharmacological interventions targeting these interconnected pathways remain scarce. Fenofibrate is well-documented for its anti-inflammatory and antioxidant effects; nevertheless, its influence on microglial lipid metabolism and ferroptotic signaling remains unexplored. The present study was designed to examine the effects of fenofibrate on lipid remodeling, oxidative stress, and ferroptosis in human HMC3 microglia activated with lipopolysaccharide (LPS) and interferon-γ (IFN-γ). HMC3 cells were pre-treated with fenofibrate followed by inflammatory activation. Cell viability, cytokine secretion, oxidative stress, lipid droplet (LD) accumulation, and ferroptosis-associated markers were analyzed by ELISA, fluorescence imaging, qRT-PCR, and Western blotting. Fenofibrate decreased the production of TNF-α, IL-1β, and IL-6, restored mitochondrial membrane potential, and suppressed ROS and malondialdehyde (MDA) generation while increasing intracellular glutathione (GSH). The treatment markedly decreased LD accumulation by downregulating the lipid metabolism-related enzymes PLIN2, DGAT1, and GPAT4. Functional assays demonstrated enhanced fatty acid oxidation and restored lipolysis, directly confirming reprogrammed lipid catabolism. Moreover, fenofibrate attenuated ferroptotic stress, evidenced by reduced intracellular Fe²⁺ levels, decreased ACSL4 expression, and significant increase of the ferroptosis-protective enzyme GPX4. These molecular changes were accompanied by improved cell survival and decreased oxidative damage, suggesting that fenofibrate may partially modulate metabolic and and redox balance in activated microglia under in vitro conditions. In conclusion, these findings suggest that fenofibrate may exert protective effects by modulating lipid metabolism and suppressing ferroptosis-related pathways in activated microglia.
USP53 regulates the AMPK pathway by deubiquitinating TJP2 to control the keloid-derived fibroblasts proliferation, invasion, and telomerase activity.
Li J, Jiang Y, He B … +3 more , Liu Z, Shi Y, Zhai X
Mol Cell Biochem · 2026 Jun · PMID 42048027 · Publisher ↗
Keloid formation originates from the abnormal activation of fibroblasts, which differentiate into myofibroblasts and excessively secrete collagen, leading to dysregulated deposition of extracellular matrix (ECM) and tiss...
Keloid formation originates from the abnormal activation of fibroblasts, which differentiate into myofibroblasts and excessively secrete collagen, leading to dysregulated deposition of extracellular matrix (ECM) and tissue fibrosis. We aim to explore the role and the mechanism of USP53 in keloid-derived fibroblasts (KFs) proliferation, invasion, and telomerase activity. Bioinformatics analysis was performed to obtain the genes differentially expressed between keloid tissue and normal tissue, as well as the enriched pathways. The KFs were isolated and transfected with USP53 silencing and overexpression plasmids. KFs proliferation, apoptosis, EMT and telomerase properties were explored. The protein expression of CDK1, Collagen I, E-cadherin, Snail, Slug, Cleaved-Caspase 3, and Caspase 3 was examined by western blotting. The interaction between USP53 and TJP2 was explored by Co-IP, and the rescue experiment was also performed. Finally, the in vivo experiments of keloid in nude mice was conducted. USP53 was downregulated in keloid tissues. Knockdown of USP53 promoted the proliferation, epithelial–mesenchymal transition (EMT), and telomerase activity, while inhibiting cell apoptosis in KFs. In contrast, USP53 overexpression exerted opposite effects. USP53 could interact with TJP2. Overexpression of USP53 led to slower TJP 2 degradation, and USP53 enhanced the stability of TJP 2. Moreover, USP53 activated the AMPK pathway. USP53 inhibited cell proliferation in vivo. USP53 regulates the AMPK pathway by deubiquitinating of TJP2 and inhibits the KFs proliferation, invasion, and telomerase activity.
Nuclear factor I-C as a novel candidate regulator in postoperative atrial fibrillation: integrated omics and proof-of-concept validation.
Gao C, Shu Y, Luo L … +5 more , Wang N, Wang T, Ren Z, Shen P, Liu Y
Mol Cell Biochem · 2026 Jun · PMID 42048026 · Publisher ↗
Postoperative atrial fibrillation (POAF) is a frequent complication of cardiac surgery, yet the upstream transcriptional regulators driving the pro-arrhythmic substrate remain unexplored. We aimed to identify and validat...
Postoperative atrial fibrillation (POAF) is a frequent complication of cardiac surgery, yet the upstream transcriptional regulators driving the pro-arrhythmic substrate remain unexplored. We aimed to identify and validate key transcription factors associated with POAF susceptibility. We performed cross-cohort integration of two independent human atrial transcriptomic datasets and applied machine learning (LASSO and SVM-RFE) to prioritize candidate genes. Transcriptional targets were predicted using the TRRUST database and protein-protein interaction (PPI) network analysis. Cellular localization was resolved using murine atrial scRNA-seq data. In vivo functional validation and biochemical signaling assays were performed in a spontaneous POAF (sPOAF) mouse model using AAV9-mediated NFIC overexpression. Nuclear Factor I-C (NFIC) was identified as a robust candidate regulator, showing consistent downregulation in human POAF cohorts and sPOAF mice. By intersecting predicted NFIC targets with the PI3K/Akt pathway, hepatocyte growth factor (HGF) was nominated as a putative downstream effector. Single-cell profiling localized NFIC and HGF predominantly to the atrial fibroblast lineage, where both were significantly downregulated in POAF. In the sPOAF model, p-AKT/AKT ratios were significantly reduced during the acute postoperative phase. Critically, AAV9-mediated NFIC restoration significantly decreased POAF incidence by 50%. Our findings identify NFIC as a novel candidate transcriptional regulator associated with POAF. These data support a working model involving a fibroblast-centered NFIC-HGF-PI3K/AKT axis, providing a fresh framework for understanding the upstream control of the postoperative atrial microenvironment.
The renoprotective effect of d-limonene against cisplatin-induced acute kidney injury: targeting Nrf2/HO-1 and NLRP-3 inflammasome signaling pathways.
Mohammed NA, Osman A, Taher ES … +5 more , Ibrahim MM, Badr BM, Eraky SM, Ali FEM, Mohamed EA
Mol Cell Biochem · 2026 Jun · PMID 42048025 · Full text
Cisplatin is a potent chemotherapeutic agent that causes renal injury. d-limonene, a natural monoterpene, may confer renal protection. This study evaluated whether d-limonene pretreatment could mitigate cisplatin-induced...
Cisplatin is a potent chemotherapeutic agent that causes renal injury. d-limonene, a natural monoterpene, may confer renal protection. This study evaluated whether d-limonene pretreatment could mitigate cisplatin-induced nephrotoxicity. Wistar rats were divided into groups receiving vehicle, d-limonene (50 or 100 mg/kg), cisplatin (7.5 mg/kg, i.p.), or cisplatin plus d-limonene (50 or 100 mg/kg). d-limonene was administered orally once daily for 14 days, starting 7 days before and continuing 7 days after the single cisplatin injection on day 7, thus acting as both pre- and post-treatment (peri-cisplatin regimen). Cisplatin induced nephrotoxicity, shown by elevated serum urea, creatinine, uric acid, cystatin C, urine KIM-1, albumin/creatinine, and renal oxidative stress markers. It downregulated Nrf2/HO-1 and upregulated NADPH oxidase and NLRP3 inflammasome, with tubular damage histologically. d-limonene pretreatment dose-dependently improved renal dysfunction, oxidative stress, and suppressed NADPH oxidase, NLRP3, and IL-1β expression. High-dose d-limonene normalized most parameters, improved kidney histology, and renal somatic index. d-limonene mitigates cisplatin-induced nephrotoxicity with associated antioxidant and anti-inflammatory effects.
The central role of mitochondrial dysfunction in neurodegeneration: implications for therapy.
Raafat MA, Al-Hasnaawei S, Mousa HM … +5 more , Hanumanthayya M, Sahoo S, Prathiba S, Singh G, Sinha A
Mol Cell Biochem · 2026 Apr · PMID 42043769 · Publisher ↗
Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis, remain leading causes of disability and premature death. Althou...
Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis, remain leading causes of disability and premature death. Although they present with distinct clinical phenotypes, they converge on several pathogenic processes. Among these, mitochondrial dysfunction has emerged as a key driver of neurodegeneration, encompassing impaired bioenergetic capacity, disturbed calcium handling, altered mitochondrial dynamics, insufficient mitophagy, and excessive production of reactive oxygen species (ROS). This review provides a focused synthesis of the ways in which mitochondrial pathology contributes to neurodegeneration across major neurodegenerative disorders and summarizes therapeutic strategies designed to target mitochondria. We outline disease-relevant mitochondrial abnormalities and connect them to neuronal loss, synaptic failure, and neuroinflammatory cascades, with particular attention to mitochondrial ROS and inflammatory signaling linked to mitochondrial DNA. The manuscript further evaluates current and emerging interventions, including mitochondria-targeted antioxidants, mitochondrial transfer/transplantation, exercise, dietary approaches, and nanotechnology-enabled delivery systems. For each strategy, we consider the mechanistic rationale, key preclinical findings, and barriers to translation. Across experimental models, many of these approaches confer measurable neuroprotection-often reflected by lower oxidative burden, stabilization of mitochondrial membrane potential, and partial restoration of ATP production. However, clinical findings have been inconsistent, suggesting that efficacy depends strongly on disease stage, patient heterogeneity, and the specific mitochondrial defect being targeted. By integrating mechanistic insights with therapeutic evidence, this review offers a structured perspective on shared and disease-specific features of mitochondrial dysfunction and highlights priorities for advancing mitochondria-centered interventions toward meaningful clinical benefit.
Regulation of sepsis-associated acute kidney injury by ELAVL1 through USP14/NCOA4-mediated ferroptosis in renal tubular epithelial cells.
Zhu X, Zheng P, Jin H … +5 more , Zhao Q, Kong K, Zheng L, Huang X, Zheng M
Mol Cell Biochem · 2026 May · PMID 42043768 · Publisher ↗
Sepsis-associated acute kidney injury (SA-AKI) is a serious complication of sepsis, characterized by elevated morbidity and mortality rates. Understanding the underlying mechanism is essential for the development of effe...
Sepsis-associated acute kidney injury (SA-AKI) is a serious complication of sepsis, characterized by elevated morbidity and mortality rates. Understanding the underlying mechanism is essential for the development of effective therapies. The aim of this study was to investigate the role and mechanism by which ELAVL1 modulates SA-AKI. The cecal ligation and puncture (CLP) mouse model and LPS-induced HK-2 cells were utilized to investigate the regulatory role of ELAVL1 in ferroptosis and kidney damage. RNA immunoprecipitation (RIP) and RNA pull-down assays were performed to analyze the interaction between ELAVL1 and USP14. Additionally, Co-IP and IP/ubiquitination assays were conducted to investigate the interaction between USP14 and NCOA4. Knockdown of ELAVL1 significantly reduced serum creatinine and BUN levels, and histological analysis revealed less tubular damage in septic mice. Moreover, the knockdown of ELAVL1 decreased lipid peroxidation (MDA), intracellular iron (Fe²⁺), LDH, and 4-HNE levels, while increasing GSH and GPX4 levels in CLP mice. In LPS-treated HK2 cells, ELAVL1 knockdown also inhibited ferroptosis. Mechanistically, ELAVL1 bound to USP14 mRNA, enhancing its stability and expression, which in turn stabilized NCOA4 via deubiquitination. Overexpression of USP14 or NCOA4 partially mitigated the inhibitory effects of ELAVL1 knockdown on ferroptosis-related markers in LPS-stimulated HK2 cells, including MDA, Fe²⁺, GSH, LDH, GPX4, lipid ROS, and cell viability. Targeting the ELAVL1/USP14/NCOA4 axis effectively reduces ferroptosis and alleviates SA-AKI, offering a promising therapeutic strategy for sepsis-induced kidney damage.
Targeting YAP: mechanistic breakthroughs and therapeutic prospects in reversing organ fibrosis.
Fu K, Cao M, Wang Y … +2 more , Luo J, Yuan W
Mol Cell Biochem · 2026 Apr · PMID 42008043 · Publisher ↗
Fibrosis, a critical global health challenge, is primarily characterized by pathological scar formation due to an imbalance in tissue injury repair mechanisms, ultimately leading to progressive organ dysfunction. Notably...
Fibrosis, a critical global health challenge, is primarily characterized by pathological scar formation due to an imbalance in tissue injury repair mechanisms, ultimately leading to progressive organ dysfunction. Notably, the Yes-associated protein (YAP), a central effector molecule in the Hippo signaling pathway, serves as a pivotal molecular regulator across fibrotic processes in multiple organs. Aberrant YAP activation is a hallmark of fibrosis in multiple organs, including the liver, kidney, heart, and lung, where it drives pro-fibrotic gene expression. Although basic research has highlighted YAP's essential role in fibrotic diseases, translating these insights into clinical applications remains complex. The current repertoire of targeted therapeutic options for fibrosis is restricted, further complicated by variations in tissue-specific responses to YAP modulation. This highlights the urgent need for a thorough analysis of the YAP regulatory network. In this review, we analyze the YAP protein interaction network to clarify the dynamic regulation of its nuclear-cytoplasmic trafficking. Furthermore, we explore the distinct signaling characteristics of YAP during organ fibrosis, summarize recent developments in anti-fibrotic strategies targeting YAP, and assess the translational potential of intervening in YAP and its upstream and downstream pathways for effective anti-fibrotic therapy.
Correction: METTL5 promotes tumor progression and ferroptosis resistance via MGST1 in HCC.
Ji T, Miao X, Fang Y … +5 more , Nie J, Zhu Q, Zhu P, Liao W, Yang D
Mol Cell Biochem · 2026 May · PMID 41989692 · Publisher ↗
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Pro-inflammatory LPS drives production and release of the chemokine MCP-1 in human coronary artery smooth muscle cells.
Bankell E, Gidlöf O, Nilsson BO
Mol Cell Biochem · 2026 May · PMID 41964752 · Full text
The chemokine monocyte chemoattractant protein-1 (MCP-1) plays an important role as chemoattractant for monocytes in atherosclerosis. It is established that MCP-1 is produced by vascular smooth muscle cells, but the unde...
The chemokine monocyte chemoattractant protein-1 (MCP-1) plays an important role as chemoattractant for monocytes in atherosclerosis. It is established that MCP-1 is produced by vascular smooth muscle cells, but the underlying mechanisms for its release are not identified. Here, we investigate production and secretion of MCP-1 in primary human coronary artery smooth muscle cells. We demonstrate that the cells express MCP-1 using RT-qPCR, immunocytochemistry and ELISA, and the ELISA analysis shows that they contain high basal levels of MCP-1 compared to human THP-1 monocytes included as positive control representing an immune cell. Immunocytochemistry discloses co-staining for MCP-1 and the ER marker calreticulin, suggesting that they may co-exist. The cellular production of MCP-1 is stimulated by the bacterial endotoxin LPS demonstrated both on mRNA and protein levels. Conditioned medium contains higher amounts of MCP-1 than fresh medium, and pro-inflammatory LPS and TNF-α stimulate release of MCP-1 from the cells. LPS does not enhance the secretion of MCP-1 at an early time point (60 min) neither in the presence nor in the absence of protein synthesis inhibition with cycloheximide, and it has no effect on intracellular [Ca2+] within 0–60 min, suggesting that LPS has no direct effect on the secretory process of MCP-1. We conclude that human coronary artery smooth muscle cells contain high levels of MCP-1, and that pro-inflammatory stimulus triggers secretion of this important chemokine indirectly via activation of MCP-1 production.
GMFB promotes lung adenocarcinoma progression by activating the MAPK/ERK signaling pathway.
Ma L, Li J, Yu W … +2 more , Li R, Si L
Mol Cell Biochem · 2026 May · PMID 41964751 · Publisher ↗
BACKGROUND: Lung adenocarcinoma (LUAD) is a highly malignant tumor with a dismal prognosis worldwide. Glial maturation factor β (GMFB), initially identified as a regulator of glial cell development, has recently been imp...
BACKGROUND: Lung adenocarcinoma (LUAD) is a highly malignant tumor with a dismal prognosis worldwide. Glial maturation factor β (GMFB), initially identified as a regulator of glial cell development, has recently been implicated in tumor microenvironment-mediated carcinogenesis. This study aims to validate the role of GMFB in LUAD progression and explore its potential as a novel biomarker and therapeutic target. METHODS: GMFB expression was evaluated in LUAD tissues and cell lines using bioinformatics analysis, immunohistochemistry (IHC), Western blotting (WB), and quantitative real-time PCR (qRT-PCR). In vitro functional assays (CCK-8, EdU, colony formation, transwell, wound healing) and a nude mouse subcutaneous tumor model were used to assess the effects of GMFB on cell proliferation and migration. RNA sequencing and bioinformatics were employed to identify downstream pathways, with rescue experiments confirming mechanistic insights. RESULTS: GMFB was significantly overexpressed in LUAD tissues and cell lines, and high GMFB expression was associated with poor patient survival. Functional studies showed that GMFB knockdown attenuated LUAD cell proliferation and migration, whereas GMFB overexpression promoted these phenotypes. In vivo experiments confirmed GMFB-driven tumor growth. Mechanistically, RNA sequencing and WB analysis revealed that GMFB activated the MAPK/ERK signaling pathway, and pharmacological inhibition of ERK reversed GMFB-mediated tumor progression. CONCLUSIONS: GMFB promotes LUAD progression by activating the MAPK/ERK pathway, positioning it as a potential biomarker and therapeutic target for LUAD diagnosis and treatment.
Inhibition of NCOA4-mediated ferritinophagy improves cardiac remodeling in diabetic cardiomyopathy via MITOL/parkin signaling.
Lu L, Liu Y, Shao Y … +4 more , Xiong X, Zhai M, Yang J, Yang L
Mol Cell Biochem · 2026 May · PMID 41964750 · Publisher ↗
Diabetic cardiomyopathy (DCM) is a diabetes mellitus-induced pathophysiological condition caused by unfavorable myocardial sequelae, with more severe cardiac dysfunction observed in patients with diabetes than in those w...
Diabetic cardiomyopathy (DCM) is a diabetes mellitus-induced pathophysiological condition caused by unfavorable myocardial sequelae, with more severe cardiac dysfunction observed in patients with diabetes than in those without diabetes. Recently, ferroptosis has been implicated in DCM; however, its role in DCM remains incompletely elucidated. This study was conducted to examine the impact of mitochondrial ubiquitin ligase (MITOL/March5) and the mitophagy receptor Parkin on DCM-induced cardiac dysfunction, as well as the effect of ferritinophagy. Wild-type and db/db mice were fed normal chow or a high-fat diet and subjected to streptozotocin treatment. Cardiac geometry and function, as well as ferroptosis-related biomarkers, were assessed upon completion of experiments. Our findings revealed that DCM induced notable alterations in cardiac geometry by increasing myocardial fibrosis and ferroptosis, involving increased reactive oxygen species production and lipid accumulation. Nuclear receptor coactivator 4 (NCOA4)-related ferroptosis was significantly activated, whereas Parkin-dependent mitophagy was dramatically inhibited. However, adeno-associated virus (AAV)-MITOL treatment markedly attenuated cardiac dysfunction and ferroptosis with those in the DCM group. Furthermore, Ad Parkin alleviated NCOA4-mediated ferroptosis and suppressed myocardial apoptosis compared with those in the high-glucose/high-fat group. Our in vitro analysis demonstrated that MITOL inhibition compromised cardiomyocyte function and elicited mitochondrial injury and lipid peroxidation, the effects of which were negated by Parkin activation. This study underscores the pivotal protective role of the MITOL/Parkin signaling pathway against DCM-induced cardiac dysfunction in NCOA4-mediated ferritinophagy.
Regulation of EMT and cholangiocarcinoma metastasis by KIN17 through the mTOR signaling pathway.
Yang Y, Luo Q, Huang C … +5 more , Lin X, Chu LT, Li Q, Tang J, Zeng T
Mol Cell Biochem · 2026 May · PMID 41964749 · Publisher ↗
KIN17 is a DNA- and RNA-binding protein involved in the regulation of several human cancers. However, its role in cancer progression and metastasis in cholangiocarcinoma remains largely unknown. In this work, the express...
KIN17 is a DNA- and RNA-binding protein involved in the regulation of several human cancers. However, its role in cancer progression and metastasis in cholangiocarcinoma remains largely unknown. In this work, the expression of KIN17 in CCA patients was investigated using bioinformatics and immunohistochemical staining. The effects of KIN17 on CCA cells’ migration and invasion were examined by scratch assay and transwell assay. In RBE and HCCC-9810 cells, knockdown of KIN17 significantly suppressed the migration and invasion ability of the cells and also inhibited the mTOR pathway, while overexpression of KIN17 promoted the migration and invasion ability of HUCCT-1 cells and stimulated the mTOR pathway, as well as genes involved in epithelial-mesenchymal transition. These findings indicate that expression of KIN17 in CCA is abnormal compared to the normal conditions and promotes the invasion and migration of CCA cells. Meanwhile, we hypothesize that KIN17 affects the migration and invasion of CCA cells through the regulation of mTOR and EMT signaling pathways. Hence, we propose KIN17 to be a novel diagnostic biomarker and therapeutic target for CCA.
PRSS23 functions downstream of ZEB1 to promote esophageal squamous cell carcinoma progression by driving M2 polarization of tumor associated macrophages.
Chen W, Chen C, Hu Z … +3 more , Li F, Peng Y, Zhang M
Mol Cell Biochem · 2026 May · PMID 41961204 · Publisher ↗
Esophageal squamous cell carcinoma (ESCC) is a common digestive tract tumor influenced by tumor-associated macrophages (TAMs), which promote progression through M2 polarization. Analysis of GSE75241 showed that PRSS23 wa...
Esophageal squamous cell carcinoma (ESCC) is a common digestive tract tumor influenced by tumor-associated macrophages (TAMs), which promote progression through M2 polarization. Analysis of GSE75241 showed that PRSS23 was significantly upregulated in ESCC samples compared with non-tumors (n = 15). Its high expression corresponded to poorer overall survival in macrophages-enriched ESCC patients (Log-rank p = 0.04). Furthermore, PRSS23 expression was elevated in ESCC tissues compared with normal controls (n = 12) and positively correlated with CD206 expression (n = 14), suggesting a potential role for PRSS23 in ESCC progression via the regulation of TAMs. PRSS23 knockdown suppressed the malignant phenotype of ESCC cells, including proliferation, migration, and invasion. In vivo, nude mice bearing PRSS23-silenced ESCC cells developed smaller tumors with fewer M2-type TAMs. Consistently, PRSS23 knockdown impaired macrophage chemotaxis and M2 polarization in co-culture with ESCC cells. Zinc finger E-box binding homeobox 1 (ZEB1) was predicted as an upstream regulator of PRSS23. Overexpression of ZEB1 increased the transcriptional activity of the PRSS23 promoter (–1110 ~ + 15 bp) by 2.55-fold compared to the vector control, confirming ZEB1 as a positive transcriptional regulator. Notably, PRSS23 knockdown rescued the promoting effects of ZEB1 overexpression on ESCC cells and macrophage M2 polarization. Further transcriptomic analysis of macrophages suggested that PRSS23 mediates M2 polarization through the Wnt/β-catenin pathway. Accordingly, PRSS23 knockdown inhibited both Wnt/β-catenin signaling and M2 polarization in co-cultured macrophages, effects that were reversed by the Wnt/β-catenin agonist SKL2001. Collectively, our findings showed that the ZEB1/PRSS23 axis promotes ESCC progression by driving M2 polarization of TAMs, offering a potential therapeutic target for ESCC treatment.
CREB1-ROC1 axis drives bladder cancer progression under hypoxic conditions.
Sun Z, Wang Y, You S … +8 more , Ji Q, Liu X, Bao P, Zhang H, Zhou X, Ye J, Li P, Wu Q
Mol Cell Biochem · 2026 May · PMID 41934550 · Publisher ↗
Hypoxia is a hallmark of tumor microenvironments that promotes bladder cancer (BCa). We aimed to study the upstream transfector of ROC1 on malignant oncological characteristics of BCa cells under hypoxic conditions, and...
Hypoxia is a hallmark of tumor microenvironments that promotes bladder cancer (BCa). We aimed to study the upstream transfector of ROC1 on malignant oncological characteristics of BCa cells under hypoxic conditions, and clarified the regulating mechanisms involved. The expressions of ROC1 and HIF1A were mediated by RT-qPCR and western blot. The upstream transcription factor of ROC1 was analyzed by bioinformatic analysis and examined by clinical data. The BCa cell lines (T24 and 5637) were treated CREB1 overexpression or knockdown. The hypoxia induction was conducted, and cell proliferation, apoptosis, migration and invasion were subsequently studied. The rescue experiments in vitro and in vivo were performed to explore the underlying regulating mechanism of CREB1. ROC1 was down-regulated in bladder cancer tissues and hypoxia condition. CREB1 was an upstream transcription factor of ROC1. CREB1 expression was correlated with T Stage in BCa, while ROC1expression was associated with N Stage in BCa patients. CREB1 promoted the proliferation and inhibited the apoptosis of BCa cells under hypoxia. CREB1 regulated the invasion, migration, and expressions of Bcl−2, Bax, cleaved caspased−3, MMP2, and MMP9 in BCa cells under hypoxia. Down-regulation of ROC1 reversed CREB1’s effect on BCa cells. Similarly, HIF1A knockdown also reversed CREB1’s impact on BCa cells. CREB1 promoted tumor growth in vivo and shROC1 reversed its effect. Our study indicated that CREB1-ROC1 axis is a hypoxia-responsive therapeutic target in BCa, which can provide new insights for BCa early screening, prevention and treatment.
Downregulation of miR-194-5p impairs cardiomyocyte proliferation and differentiation through targeting Fign in congenital heart disease.
Liang P, Ren G, Zhu J … +5 more , Zhou T, Chen Y, Lin J, Zhang Y, Qu X
Mol Cell Biochem · 2026 May · PMID 41934549 · Publisher ↗
Congenital heart disease (CHD) is a prevalent birth defect with complex pathogenesis. MicroRNAs (miRNAs) are crucial regulators, yet their specific roles in CHD remain largely unexplored. This study performed miRNA seque...
Congenital heart disease (CHD) is a prevalent birth defect with complex pathogenesis. MicroRNAs (miRNAs) are crucial regulators, yet their specific roles in CHD remain largely unexplored. This study performed miRNA sequencing on serum samples from CHD patients and identified a distinct profile of dysregulated miRNAs. Based on its pronounced and consistent downregulation, miR-194-5p emerged as a prominent candidate for subsequent functional validation. This downregulation was conserved in a valproic acid-induced murine CHD model, observed in both serum and cardiac tissue. Functional in vivo experiments demonstrated that knockdown of miR-194-5p in neonatal mice impaired cardiac function and suppressed cardiomyocyte proliferation. In vitro, miR-194-5p downregulation inhibited the proliferation of primary cardiomyocytes and impaired the cardiomyogenic differentiation of P19 cells, whereas its overexpression enhanced these processes. Mechanistically, bioinformatics analysis identified Fidgetin (Fign) as a direct target of miR-194-5p, confirmed by dual-luciferase reporter assay and Western blot. Crucially, the impaired proliferation and differentiation phenotypes induced by Fign overexpression were effectively rescued by miR-194-5p mimics. In conclusion, our findings revealed a novel pathogenic axis in CHD, whereby miR-194-5p downregulation impairs cardiac development by directly targeting Fign, highlighting its potential as a therapeutic target.
From copper transport to cuproptosis: emerging therapeutic targets in cardiovascular disease.
Zhang X, Liu J, He C … +4 more , Wang Y, Ni Q, Zhou Y, Sun J
Mol Cell Biochem · 2026 Apr · PMID 41925801 · Publisher ↗
Cardiovascular diseases (CVDs) continue to represent the predominant contributors to global morbidity and mortality, imposing profound clinical and socioeconomic burdens. While classical mechanisms including inflammation...
Cardiovascular diseases (CVDs) continue to represent the predominant contributors to global morbidity and mortality, imposing profound clinical and socioeconomic burdens. While classical mechanisms including inflammation, autophagy, and apoptosis have been extensively characterized, the identification of cuproptosis has introduced a novel paradigm for CVD research. Copper is fundamental to mitochondrial energy metabolism and redox homeostasis; however, its dysregulation induces pathological consequences. Mechanistically, cuproptosis is triggered by copper accumulation and its binding to lipoylated mitochondrial enzymes, which induces protein aggregation and proteotoxic stress. In this review, we aimed to delineate systemic and intracellular copper metabolism, summarize the molecular mechanisms of cuproptosis, evaluate current evidence linking copper dysregulation and cuproptosis to CVDs, and highlight therapeutic strategies and outstanding challenges. Collectively, this work provides mechanistic insights and identifies translational opportunities for targeting cuproptosis in cardiovascular medicine.
S-equol promotes ferroptosis in triple negative breast cancer by coordinating NCOA4-mediated ferritinophagy and PPARγ-mediated lipid metabolism.
Ni F, Huang Z, Cui Y … +4 more , Huang P, Xue Z, Huang G, Zhao Y
Mol Cell Biochem · 2026 May · PMID 41925800 · Publisher ↗
Triple negative breast cancer (TNBC) is a diverse and highly aggressive cancer characterized by a strong tendency to metastasize, poor prognosis, and a lack of effective therapeutic targets. S-equol, an active metabolint...
Triple negative breast cancer (TNBC) is a diverse and highly aggressive cancer characterized by a strong tendency to metastasize, poor prognosis, and a lack of effective therapeutic targets. S-equol, an active metabolinte produced by gut microbiota through the conversion of daidzein, has been proven to possess anticancer activity. This study aims to investigate the anticancer effects of S-equol on TNBC and to elucidate key targets and potential mechanisms. In vitro experiments utilized the TNBC cell lines, while in vivo experiments employed a nude mouse xenograft tumor model. By means of using CCK-8, colony formation, scratch, and transwell invasion assays, the biological function of S-equol was evaluated. In addition, bioinformatics methods were employed to explore the potential signaling pathways and target genes of S-equol. The in vitro results substantiated that S-equol significantly suppressed both the proliferation and metastatic capacity of TNBC cells. Moreover, the prediction results indicated that S-equol may exert its anti-TNBC effects through ferroptosis via the PI3K/AKT signaling pathway, with PPARγ identified as the key gene. In vitro and in vivo results collectively verified that S-equol triggers ferroptosis by influencing lipid peroxidation and Fe² levels, thereby suppressing the proliferation of TNBC. In terms of mechanism, the result that S-equol enhanced the sensitivity of TNBC to ferroptosis ensued from inhibiting the PI3K/AKT/mTOR pathway. This inhibition suppressed the reduction in lipid peroxidation mediated by PPARγ and GPX4, while promoting an increase in intracellular Fe² levels mediated by NCOA4, which were respectively reversed by PPARγ and STAT3 agonists, as well as autophagy inhibitor ULK101. The results of NCOA4 knockdown or PPARγ overexpression further verified the previous mechanism of S-equol. In conclusion, these findings revealed that S-equol promotes ferroptosis in TNBC by suppressing PPARγ-mediated lipid metabolism and promoting NCOA4-mediated ferritinophagy, which was largely dependent on the regulation of the PI3K/AKT/mTOR signaling pathways.
Dexmedetomidine inhibits microglia activation, neuroinflammation, and glycolysis in postoperative cognitive dysfunction by promoting YTHDF2-mediated PKM2 mRNA degradation.
Li Q, Wang H, Chen N … +5 more , Liu X, Li Y, Chen L, Gan L, Luan Y
Mol Cell Biochem · 2026 May · PMID 41925799 · Publisher ↗
Postoperative cognitive dysfunction (POCD) is a common complication following surgery, particularly in elderly patients, and is closely linked to neuroinflammation driven by microglial activation. While dexmedetomidine (...
Postoperative cognitive dysfunction (POCD) is a common complication following surgery, particularly in elderly patients, and is closely linked to neuroinflammation driven by microglial activation. While dexmedetomidine (Dex) has shown neuroprotective potential in clinical settings, the molecular mechanisms underlying its beneficial effects—particularly in relation to RNA epigenetic regulation and metabolic reprogramming in microglia—remain poorly understood. Here, we uncover a novel mechanism by which Dex alleviates POCD through modulation of N6-methyladenosine (m6A)–dependent post-transcriptional regulation of pyruvate kinase M2 (PKM2). We demonstrate that Dex enhances the expression of the m6A reader protein YTHDF2, which recognizes m6A-modified PKM2 mRNA and promotes its degradation, thereby suppressing microglial glycolysis and neuroinflammation. In both in vitro and in vivo models, Dex treatment reversed surgery- or LPS-induced cognitive deficits, reduced pro-inflammatory cytokine production, and normalized metabolic shifts in microglia—effects that were dependent on YTHDF2-mediated PKM2 downregulation. Our findings uncovered a novel epigenetic mechanism by which Dex exerts neuroprotection and highlight YTHDF2-mediated PKM2 regulation as a potential therapeutic target for POCD.
Targeting PSAT1 in diabetic kidney disease: a ferroptosis-driven strategy for precision therapy.
Wei Y, Yuan C, Lu D … +2 more , Xiang Y, Ni L
Mol Cell Biochem · 2026 May · PMID 41925798 · Publisher ↗
Diabetic kidney disease (DKD) involves mitochondrial dysfunction and ferroptosis, yet the convergence of these processes at the gene level remains unclear. We first analyzed human renal transcriptomic data (GSE30528) to...
Diabetic kidney disease (DKD) involves mitochondrial dysfunction and ferroptosis, yet the convergence of these processes at the gene level remains unclear. We first analyzed human renal transcriptomic data (GSE30528) to identify differentially expressed genes (DEGs). DEGs associated with both mitophagy and ferroptosis (DEMFRGs) were extracted. Protein-protein interaction (PPI) networks, the MCC algorithm, and LASSO regression were used to screen hub genes. Immune infiltration was assessed via CIBERSORT. Diagnostic performance of hub genes was evaluated using ROC curves in GSE30528 and validated in an independent dataset (GSE96804). Experimental validation was conducted in a high-fat diet/STZ-induced DKD mice and high-glucose-treated HK-2 cells. Drug prediction were predicted by Network Analyst platform with DrugBank. Molecular docking for drug prediction was performed using AutoDock Vina. We identified 12 DEMFRGs, of which 9 were hub genes (DUSP1, ASNS, FBXW7, HMOX1, NFE2L2, SIRT1, STEAP3, PSAT1, PIK3CA). Enrichment analysis linked them to ferroptosis and the PI3K-Akt pathway. PSAT1 emerged as a novel, dual-pathway regulator, significantly correlated with immune cell infiltration (e.g., Eosinophils, r = 0.46). A prognostic model based on the 9 hub genes achieved an AUC of 1.000 (GSE30528 and GSE96804). PSAT1 is predominantly localized to renal tubules, which is validated by both experimental studies and box plots from GSE21785 datasets. PSAT1 exhibited strong diagnostic power (AUC = 0.79) and was experimentally confirmed to be upregulated in DKD models and Nephroseq V5 database. Molecular docking demonstrated strong binding of Pyridoxal phosphate and L-Glutamate to PSAT1(binding energy: -7.0 kcal/mol and − 5.7 kcal/mol). This study provides the first integrative analysis linking mitophagy and ferroptosis in DKD, identifies key PSAT1 gene and immune interactions, and proposes druggable targets, laying the groundwork for precision therapeutics in DKD.
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