Molecular And Cellular Biochemistry[JOURNAL]
Sun
200 papers
Identification of disease-associated gene expression signatures for mechanistic insights and drug prediction in dilated cardiomyopathy-induced heart failure.
Yu W, Xu S, Tan X … +8 more , Zhang H, Ma R, Zeng Y, Xu A, Tang H, Rui Q, Song Y, Zhou Y
Mol Cell Biochem · 2026 Mar · PMID 41569495 · Publisher ↗
Dilated cardiomyopathy (DCM)-induced heart failure (HF) remains a major global health burden, highlighting the need to identify disease-associated molecular signatures and potential therapeutic targets. In this study, we...
Dilated cardiomyopathy (DCM)-induced heart failure (HF) remains a major global health burden, highlighting the need to identify disease-associated molecular signatures and potential therapeutic targets. In this study, we performed differential expression analysis and weighted gene co-expression network analysis (WGCNA) on the GSE141910 dataset, which identified 138 genes associated with DCM-induced HF. These were further refined to 48 candidate genes using support vector machine-recursive feature elimination (SVM-RFE). Protein-protein interaction (PPI) network analysis revealed 10 hub genes, and external validation identified four core genes—MFAP4, CCDC80, LTBP2, and COL16A1—that were consistently upregulated in DCM-induced HF. Single-cell and functional enrichment analyses indicated that these genes are predominantly expressed in cardiac fibroblasts and may contribute to myocardial fibrosis by activation of the NOTCH signaling pathway. Drug screening suggested beta-naphthoflavone as a potential therapeutic compound. In vivo validation confirmed the upregulation of the core genes through RT-qPCR, western blot, and immunohistochemistry in an isoproterenol (ISO)-induced HF mouse model. In summary, MFAP4, CCDC80, LTBP2, and COL16A1 represent disease-associated transcriptional signatures and potential therapeutic targets for DCM-induced HF, offering novel insights into disease mechanisms and treatment strategies.
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 Mar · PMID 41557129 · Publisher ↗
PURPOSE: Hepatocellular carcinoma (HCC) ranks among the most prevalent cancers globally. Ferroptosis plays a vital role in the resistance of HCC to various cancer treatments. However, the specific molecular mechanisms th...
PURPOSE: Hepatocellular carcinoma (HCC) ranks among the most prevalent cancers globally. Ferroptosis plays a vital role in the resistance of HCC to various cancer treatments. However, the specific molecular mechanisms that inhibit ferroptosis in HCC remain unknown. Therefore, this study aims to elucidate the role of 5, N6-adenosine (METTL5) in regulating HCC development and ferroptosis. METHODS: Quantitative real-time polymerase chain reaction, western blotting, and immunohistochemical staining were employed to detect the expression of METTL5 and Microsomal glutathione S-transferase 1 (MGST1) in HCC cell lines and clinical samples. Xenotransplantation experiments were conducted to investigate the effects of METTL5 knockdown on HCC cells in vivo. Tandem mass tagging proteomic quantification was utilized to analyze the downstream targets of METTL5. In vitro functional rescue assays were used to explore the influence of METTL5 and MGST1 on cell functions, including proliferation, migration, invasion, and ferroptosis in HCC cell lines. RESULTS: METTL5 and MGST1 were aberrantly and highly expressed in HCC tissues than in adjacent normal liver tissues. High expression levels of METTL5 or MGST1 were a prognostic risk factor for patients with HCC. METTL5 regulated the protein expression of MGST1 through its N6-methyladenosine catalytic function. The METTL5-MGST1 axis regulated proliferation, migration, invasion, and suppression of ferroptosis in HCC cells. CONCLUSION: Our study explored and confirmed the oncogenic roles of METTL5 and MGST1 in HCC, uncovering a novel mechanism by which the METTL5-MGST1 axis suppresses ferroptosis in HCC. Our findings establish a molecular foundation for developing therapeutic strategies for HCC.
Advances in MicroRNA-Based Therapies for Cardiac Repair: Emerging Strategies for Treating Myocardial Infarction.
Iqbal A, Ghani MW, Shao N … +3 more , Zhang Y, Wang Z, Pei R
Mol Cell Biochem · 2026 Apr · PMID 41557128 · Publisher ↗
Myocardial infarction (MI) continues to be a major cause of mortality worldwide, highlighting the need for immediate investigation into novel therapeutic approaches for repairing damaged heart tissue. MicroRNAs (miRNAs)...
Myocardial infarction (MI) continues to be a major cause of mortality worldwide, highlighting the need for immediate investigation into novel therapeutic approaches for repairing damaged heart tissue. MicroRNAs (miRNAs) have become essential regulators of different biological processes, including heart development, MI development, and cardiac repair after MI. This review seeks to elucidate the complex functions of miRNAs in MI development and cardiac regeneration/repair after MI, emphasizing their role in regulating different stages related to MI, such as inflammation, apoptosis, angiogenesis, and fibrosis. We also reviewed the advances in the regulation of particular miRNAs in the MI and their potential as therapeutic agents for evaluating cardiac recovery. Furthermore, we summarised the encouraging developments in miRNA-based therapeutics, in vitro growth of cardiomyocytes (CMs) for cell therapy of MI. Understanding the various functions that miRNAs perform in the heart's repair process following MI offers a great deal of promise for developing therapeutic approaches that can improve patient outcomes and mitigate the effects of heart failure.
Therapeutic potential of umbilical cord-derived mesenchymal stem/stromal cells versus their conditioned media on treatment of polycystic ovary In-vivo.
Abou-El-Naga A, Elarby NY, Sobh MA … +1 more , Mutawa G
Mol Cell Biochem · 2026 Mar · PMID 41557127 · Publisher ↗
Polycystic ovary syndrome (PCOS) is a common endocrine and reproductive disorder affecting females of reproductive age. This study explored the therapeutic potential of umbilical cord-derived mesenchymal stem cells (UC-d...
Polycystic ovary syndrome (PCOS) is a common endocrine and reproductive disorder affecting females of reproductive age. This study explored the therapeutic potential of umbilical cord-derived mesenchymal stem cells (UC-derived MSCs) and their conditioned medium (UC-derived MSCs-CM) in a letrozole-induced PCOS rat model (n = 8 per group; four groups: control, PCOS, MSC-treated, and MSC-CM-treated). An additional subset (n = 5 per group) was used for mating studies. Various assessments were carried out, including fertility outcomes, monitoring of the estrous cycle, hormonal profiling (including testosterone, luteinizing hormone [LH], follicle-stimulating hormone [FSH], LH/FSH ratio, progesterone, estrogen, and insulin), insulin resistance index (HOMA-IR), lipid metabolism parameters (cholesterol, triglycerides, low-density lipoprotein [LDL], and high-density lipoprotein [HDL]), oxidative stress biomarkers (glutathione and malondialdehyde [MDA]), and markers of apoptosis (Annexin V/PI and Caspase-3). Histological and immunohistochemical analyses of ovarian and uterine tissues were also completed. Data were analyzed using one-way ANOVA with Tukey's post hoc test for most parameters, the Kruskal-Wallis test with Dunn's post hoc test for non-normally distributed variables, and Fisher's exact test for pregnancy rates. Results are presented as mean ± SD, and significance was set at p < 0.05. Inducing PCOS led to reproductive and metabolic problems, including high androgen levels, increased insulin levels, elevated HOMA-IR, abnormal lipid levels, heightened oxidative stress, increased apoptotic activity, and raised proinflammatory cytokine levels. Both UC-derived MSCs and UC-derived MSCs-CM treatments significantly enhanced these issues by reducing oxidative stress, lowering apoptotic and inflammatory markers, and balancing reproductive hormones. Remarkably, UC-derived MSCs treatment has shown stronger effects, restoring normal estrous cycles, improving ovarian structure, and resulting in positive pregnancy outcomes. These findings suggest that UC-derived MSCs could be a promising cell-based treatment for PCOS and that UC-derived MSCs-CM might be a safe, cell-free alternative with significant therapeutic potential.
ZNF384-regulated SLC31A1 expression promotes tumor proliferation and invasion in breast cancer.
Hong T, Li W, Wang Q … +6 more , Ye Z, Xu Y, Yang B, Chen J, Lian W, Wang C
Mol Cell Biochem · 2026 Mar · PMID 41553436 · Full text
BACKGROUND: SLC31A1, a copper transporter, has been implicated in copper metabolism processes. This study aims to explore the function and potential regulatory mechanisms of SLC31A1 in breast cancer. METHODS: The TCGA da...
BACKGROUND: SLC31A1, a copper transporter, has been implicated in copper metabolism processes. This study aims to explore the function and potential regulatory mechanisms of SLC31A1 in breast cancer. METHODS: The TCGA database was utilized to analyze SLC31A1 expression across various cancer types. SLC31A1 expression in breast cancer tissues was validated in an independent cohort of 80 paired breast cancer and adjacent normal tissues. SLC31A1 expression was manipulated in MCF-7 and BT-549 breast cancer cells using shRNA and overexpression vectors. Cell proliferation, colony formation, and invasion assays were performed to assess the functional consequences of SLC31A1 manipulation. ZNF384, a potential transcription factor for SLC31A1, was identified through bioinformatics analysis, and its binding to the SLC31A1 promoter was confirmed using dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP). RESULTS: SLC31A1 expression was significantly elevated in breast cancer tissues, and high expression was associated with poor prognosis. SLC31A1 promoted cell viability, colony formation, and invasion. ZNF384 was identified as a transcription factor that regulates SLC31A1 expression, and its overexpression enhanced SLC31A1 expression, while knockdown of ZNF384 inhibited breast cancer cell proliferation and invasion. ChIP assays confirmed a direct interaction between ZNF384 and the SLC31A1 promoter. CONCLUSION: SLC31A1 plays a crucial role in the proliferation and invasion of breast cancer cells, and its expression is regulated by ZNF384. These findings highlight SLC31A1 as a potential therapeutic target and suggest that modulation of copper metabolism may offer novel strategies for breast cancer treatment.
Correction to: Growth differentiation factor 11 attenuates doxorubicin-induced cardiotoxicity by inhibiting myocardial pyroptosis and oxidative stress.
Ye J, Liu Y, Xu F … +8 more , Sheng Y, Xu D, Yuan R, Hu X, Zhou Y, Jin T, Ye T, Zong G
Mol Cell Biochem · 2026 Apr · PMID 41525025 · Publisher ↗
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Matrine functions as a tumor inhibitor to influence proliferation, metastasis and glycolysis in colorectal cancer via depending on METTL14-mediated m6A methylation of MEX3A.
Meng T, Gao Z, Fang X … +6 more , Liu J, Hou D, Zhang L, Zuo Z, Zheng Z, Zhu S
Mol Cell Biochem · 2026 Mar · PMID 41525024 · Publisher ↗
Matrine is considered as an anti-cancer drug in a variety of cancers, including colorectal cancer (CRC). Methyltransferase-like 14 (METTL14) and Mex-3 RNA binding family member A (MEX3A) were associated with CRC progress...
Matrine is considered as an anti-cancer drug in a variety of cancers, including colorectal cancer (CRC). Methyltransferase-like 14 (METTL14) and Mex-3 RNA binding family member A (MEX3A) were associated with CRC progression. This study focused on the mechanism of matrine with METTL14 and MEX3A in CRC. Cell viability, proliferation, apoptosis, and migration/invasion were assessed by cell counting kit-8, EdU assay, flow cytometry, and transwell assay. Glycolysis metabolism was evaluated by glucose consumption and ATP/ADP ratio using kits. RT-qPCR and Western blot were employed for expression examination. Gene interaction was analyzed via methylated RNA immunoprecipitation (MeRIP) and RIP assays. The role of matrine in vivo was explored by xenograft models in mice. CRC cell proliferation, metastasis and glycolysis were restrained by matrine. METTL14 was up-regulated in matrine-treated CRC cells. Anti-tumor effects of matrine on CRC cells were associated with upregulation of METTL14. METTL14 reduced MEX3A expression by mediating the m6A modification of MEX3A, and YTHDF1 acted as a "reader" protein to affect m6A methylation of MEX3A. METTL14 suppressed CRC cell malignant progression via inhibiting MEX3A. MEX3A overexpression recused the tumor-inhibitory regulation of matrine in CRC cells. Matrine also repressed tumor growth of CRC in vivo through downregulating MEX3A. This study revealed that matrine played a cancer-suppressive role in CRC through targeting METTL14/MEX3A network, unraveling a molecular mechanism of matrine in CRC inhibition.
ANXA1 overexpression promotes B cell acute lymphoblastic leukemia progression and resistance by regulating fatty acid metabolism through PI3K/Akt signaling.
Liu P, Ma D, Pan C … +4 more , Kang Q, Wang Y, Zhang M, Wang J
Mol Cell Biochem · 2026 Mar · PMID 41525023 · Full text
Progression and chemoresistance is the main cause of acute lymphoblastic leukemia(ALL) treatment failure. However, its mechanism has not been fully understood. Herein, Annexin A1 (ANXA1) overexpression was found by bioin...
Progression and chemoresistance is the main cause of acute lymphoblastic leukemia(ALL) treatment failure. However, its mechanism has not been fully understood. Herein, Annexin A1 (ANXA1) overexpression was found by bioinformatic analysis in B-ALL cells. Clinical specimens were collected to preliminarily explore the role of ANXA1 in B-ALL. It showed that ANXA1 was obviously upregulated in bone marrow samples from B-ALL patients with chemoresistance and correlated with relapse or resistance. Then, we performed cell proliferation and apoptosis assays in CCRF-SB and Nalm6 cells lines in vitro. Overexpression of ANXA1 protected the B-ALL cells from apoptosis induced by dexamethasone and promoted cell cycle progression in vitro. We also found that ANXA1 promoted B-ALL cell proliferation, which correlated with the activated fatty acid metabolism in vitro. Moreover, the content of neutral lipids and the protein expression levels of fatty acid metabolism related ACC1 and FASN proteins were significantly decreased following downregulation of ANXA1. Additionally, high expression of ANXA1 promoted leukemia cell progression by regulating fatty acid metabolism through activating PI3K/AKT signaling pathway. Then in vivo results indicated that downregulation of ANXA1 in B-ALL cells could significantly reduce leukemic cell burden and increase dexamethasone sensitivity. Therefore, ANXA1 was identified as an oncogene in the development and progression of B-ALL and might be a promising biomarker for treating B-ALL.
Hyperglycemia alters the gene and protein expression of CDC42 in small and large intestine of Sprague-Dawley rats.
Stojanovic M, Mendoza-Mari Y, Rai V … +1 more , Agrawal DK
Mol Cell Biochem · 2026 Mar · PMID 41511725 · Full text
Diabetes mellitus (DM) is associated with gastrointestinal complications, including structural and functional changes in both small and large intestine. CDC42, a Rho GTPase, plays a critical role in maintaining epithelia...
Diabetes mellitus (DM) is associated with gastrointestinal complications, including structural and functional changes in both small and large intestine. CDC42, a Rho GTPase, plays a critical role in maintaining epithelial integrity through regulation of tight junctions and cytoskeletal organization. Moreover, CDC42 expression has been reported in inflammatory bowel disease (IBD). However, its expression patterns and regulatory mechanisms in the diabetic gut remain poorly defined, particularly in the context of DM - IBD comorbidity. Our study aimed to evaluate histological changes and CDC42 gene and protein expression in the small intestine (ileum) and large intestine (colon) of streptozotocin-induced female and male Sprague-Dawley rats. Rats were divided in control (n = 10) and diabetic (n = 12) group. Histological analysis was based on hematoxylin-eosin staining sections. CDC42 gene and protein expression were quantified using RT-qPCR, western blotting, and immunofluorescence. Correlation analyses were performed to examine the relationship between CDC42 gene expression and clinical parameters, including blood glucose levels and weight gain, stratified by gender. Histological examination revealed marked inflammatory cell infiltration in both intestinal segments (ileum and colon). CDC42 gene expression was significantly increased in the small and large intestine of diabetic rats, particularly in females (for small intestine p < 0.001; for large intestine p < 0.01), suggesting a gender-specific response potentially mediated by hormonal regulation. Reduced expression of CDC42 was detected at protein level in the colon (p < 0.001). These findings highlight a differential expression of CDC42 in the small and large intestine under diabetic conditions. Since CDC42 expression in our study has been found to be related to the intestinal changes under diabetic conditions, future research should be directed towards CDC42 modulation to reduce the pathological changes in the intestine. Getting better insight in CDC42 molecular pattern related to IBD and DM, and development of strategies for its modulation, could be beneficial in clinical setting to control both IBD and DM disease progression.
Hyperglycemia impairs the expression of inflammatory mediators in rat intestine: an implication for intestinal inflammation and inflammatory bowel disease.
Maličević U, Rai V, Skrbic R … +1 more , Agrawal DK
Mol Cell Biochem · 2026 Mar · PMID 41511724 · Full text
Diabetes mellitus and inflammatory bowel disease are chronic inflammatory disorders characterized by immune dysregulation and rising global prevalence. Epidemiological studies increasingly suggest a bidirectional associa...
Diabetes mellitus and inflammatory bowel disease are chronic inflammatory disorders characterized by immune dysregulation and rising global prevalence. Epidemiological studies increasingly suggest a bidirectional association between the two conditions, linked through shared mechanisms of intestinal barrier dysfunction, microbial dysbiosis, and sustained innate immune activation. Activated macrophages play a central role in driving mucosal inflammation through polarization toward a pro-inflammatory M1 phenotype, accompanied by increased production of inflammatory cytokines. These mediators disrupt tight junctions, induce epithelial apoptosis, and perpetuate cycles of immune activation and tissue injury. This macrophage-cytokine axis not only amplifies local inflammation but also sustains chronic barrier dysfunction, creating a pathogenic overlap between diabetes mellitus-associated intestinal injury and intestinal bowel disease. In this study, we used a low dose streptozotocin and high-fat diet-induced diabetic Sprague-Dawley rat model in both sexes to investigate the effects of chronic hyperglycemia on intestinal inflammation, with particular emphasis on macrophage activation and pro-inflammatory cytokine responses. We found inflammation in both small and large intestines with mucosal injury and barrier disruption, and immune activation involving macrophages and enhanced expression of CD68, iNOS, TNF-α, and IL-6. Female rats were more susceptible to gut-related inflammatory changes due to diabetes. These findings suggest a complex interplay between epithelial stress, immune signaling, and microbial factors supporting the role of intestinal inflammation in the immune-metabolic interaction in diabetes-associated intestinal changes, which may contribute to the pathogenesis of inflammatory bowel disease.
Advances in natural compounds modulating autophagy for the therapeutic intervention of heart failure.
Tang J, Zhou C, Li M … +5 more , Tao J, Deng R, Ouyang X, Zhang G, Liu H
Mol Cell Biochem · 2026 Mar · PMID 41511723 · Full text
Heart failure (HF) represents the terminal stage of multiple cardiovascular disorders and is characterized by substantial morbidity, disability, and mortality. Although standard pharmacotherapies offer partial symptomati...
Heart failure (HF) represents the terminal stage of multiple cardiovascular disorders and is characterized by substantial morbidity, disability, and mortality. Although standard pharmacotherapies offer partial symptomatic relief, their capacity to halt or reverse disease progression remains limited. In recent years, autophagy-an essential intracellular degradation and recycling process that safeguards cardiomyocyte homeostasis-has emerged as a critical determinant in the onset and progression of HF. In this review, we systematically examined approximately 170 research articles related to "natural compounds-autophagy-HF" published up to 2025, and synthesized major advances reported over the past five years. Based on chemical structure and natural source, representative bioactive compounds were categorized into five major classes: flavonoids, polyphenols, alkaloids, terpenoids, and marine-derived molecules. We then integrated evidence on the principal autophagy-regulatory signaling cascades influenced by these compounds, including the AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) axis, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), sirtuin 1 (SIRT1)/forkhead box O (FOXO), BCL2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3)/NIP3-like protein X (NIX), and Beclin-1 pathways. Moreover, this review summarizes how these natural compounds modulate autophagy to attenuate key pathological processes associated with HF, including cardiac hypertrophy, adverse ventricular remodeling, mitochondrial dysfunction, and cardiomyocyte apoptosis. By comparing convergent mechanisms and compound-specific differences in autophagy-mediated cardioprotection, we highlight emerging mechanistic patterns and therapeutic implications. Collectively, through structured classification of compounds, integration of autophagy signaling pathways, and assessment of translational potential, this review provides a systematic framework to guide the rational application and further development of natural products for the prevention and treatment of HF.
Genetic and epidemiological insights into the role of neutrophil percentage in heart failure risk: a Mendelian randomization and NHANES study.
Gao Y, Yang F, Lei L … +3 more , Qin Y, He L, Zeng X
Mol Cell Biochem · 2026 Mar · PMID 41511722 · Publisher ↗
Systemic inflammation contributes to the progression of heart failure (HF). However, the precise effects of platelet count (PCT), white blood cell count (WBC), neutrophil percentage (NEUT) on HF development and progressi...
Systemic inflammation contributes to the progression of heart failure (HF). However, the precise effects of platelet count (PCT), white blood cell count (WBC), neutrophil percentage (NEUT) on HF development and progression are poorly understood. Thus, in this study, we aimed to assess the associations between PCT, WBC, NEUT and HF. We utilized National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2018, excluding the second round of test data from 2001 to 2002, to assess HF using questionnaires and measured blood parameters adjusted by the covariates. We employed weighted quantile sum (WQS) regression to analyze the overall impact of multiple blood markers on HF, restricted cubic spline (RCS) analysis to assess non-linear relationships, and Mendelian randomization (MR) analysis using two-sample MR methods to examine genome-wide association study data. We also further confirmed the causal direction by Steiger test. The result from WQS regression showed that significant associations between PCT, WBC, and NEUT and HF. NEUT was most strongly linked to HF (P = 0.001), with heightened risk at levels ≥ 58.507%. RCS analysis showed a non-linear relationship of HF with WBC, where higher counts caused a shift from protective to increasing risk. MR analysis revealed a significant causal relationship between NEUT and HF (P = 0.00156), which was confirmed using the Steiger test. Reverse MR analysis indicated that HF had no significant impact on NEUT (P = 0.772). Our study highlights a significant correlation between NEUT and HF, indicating that NEUT might potentially serve as a biomarker for predicting HF.
Advances in the application of spatial transcriptomics in understanding development and disease.
Li Y, Zheng QW, Li M … +2 more , Chen J, Zhao LY
Mol Cell Biochem · 2026 Mar · PMID 41511721 · Publisher ↗
Spatial transcriptomics (In this review, 'spatial transcriptomics' (ST) is employed as a overarching term, encompassing two distinct concepts. Firstly, 'tissue-level ST' refers to the capture of tissue samples at a resol...
Spatial transcriptomics (In this review, 'spatial transcriptomics' (ST) is employed as a overarching term, encompassing two distinct concepts. Firstly, 'tissue-level ST' refers to the capture of tissue samples at a resolution of 10-100 μm, encompassing 1-20 cells. Secondly, 'spatially resolved single-cell transcriptomics' (sc-ST) involves the analysis of individual cells or nuclei, with each sequencing unit measuring ≤ 2 μm) fuses high-throughput sequencing with positional information to map gene expression within intact tissues. By preserving spatial context, the technology uncovers cell types, signaling circuits and regulatory networks that drive organogenesis, differentiation and disease. Here we synthesize recent methodological advances and their application to developmental and clinical questions. The term "Spatial Transcriptomics" as used in this paper comprehensively encompasses all sequencing technologies that preserve spatial coordinates, including multimodal data such as transcriptomics (RNA), genomics (DNA), epigenomics (ATAC, CUT&Tag), and translationalomics (Ribo-seq).
Arctigenin ameliorates neointima formation induced by vascular injury by inhibiting inflammatory response and proliferation through the IL-6/JAK2/STAT3 pathway.
Zhao C, Wang Z, Chen L … +5 more , Xu Y, Sun X, Tu K, Lv L, Xue G
Mol Cell Biochem · 2026 Mar · PMID 41511720 · Publisher ↗
In-stent restenosis (ISR) is the main risk for the failure of vascular stent implantation. Arctigenin (ARCG) as the active principle of Arctium lappa, possesses the ability to regulate proliferation and inflammation. Thi...
In-stent restenosis (ISR) is the main risk for the failure of vascular stent implantation. Arctigenin (ARCG) as the active principle of Arctium lappa, possesses the ability to regulate proliferation and inflammation. This study was conducted to illuminate the role and mechanism of ARCG in ISR. The effects of ARCG on the inflammation and proliferation of vascular smooth muscle cells (VSMC) were detected. Then we profiled RNA transcript expression in the femoral arteries of restenosis patients and healthy donors along with the SwissTargetPrediction to identify the target of ARCG. VSMCs were stimulated with IL-6 to assess the effect and mechanism of ARCG in vitro, and the restenosis mouse models generated by the wire injury of the femoral arteries were used to explore the effect of ARCG on restenosis in vivo. We reported significantly increased levels of inflammation and IL-6/JAK/STAT3 pathway in tissue samples from patients with restenosis and restenosis mouse models. And ARCG inactivated the IL-6/JAK2/STAT3 pathway, inhibiting proliferation and inflammation in a dose-dependent manner. Moreover, ARCG treatment was found to inhibit intimal hyperplasia in restenosis mouse models. ARCG inhibits ISR by inhibiting proinflammatory response and proliferation of VSMCs via IL-6/JAK2/STAT3 pathway, providing a promising drug candidate for ISR.
Bone mesenchymal stem cells attenuate axonopathy in spinal cord of rats exposed to 2,5-hexanedione via NGF-dependent and -independent pathways.
Bai Q, Li Z, Chen J … +5 more , Liu M, Shao X, Chen X, Piao F, Fang L
Mol Cell Biochem · 2026 Mar · PMID 41511719 · Publisher ↗
N-hexane is a widely used aliphatic hydrocarbon solvent that can cause central-peripheral neuropathy. Compared to peripheral nerve tissue, spinal nerve tissue is more vulnerable and typically non-regenerable. However, no...
N-hexane is a widely used aliphatic hydrocarbon solvent that can cause central-peripheral neuropathy. Compared to peripheral nerve tissue, spinal nerve tissue is more vulnerable and typically non-regenerable. However, no effective treatments are currently available. Stem cells are attractive therapeutic cells because of their extensive self-renewal and pluripotent differentiation abilities. Accordingly, numerous studies are focused on their restorative potential. In the present study, we investigated the effects and mechanisms of stem cell therapy on spinal nerves damaged by 2,5-HD (a proximate toxic metabolite of n-hexane). Our results showed that spinal axonopathy induced by 2,5-HD was alleviated by bone mesenchymal stem cell (BMSC) transplantation. Further, by examining the expression of molecules associated with axonal outgrowth, NGF signaling was found to be involved in the regeneration of spinal axons. Moreover, intervention experiments showed that PTEN was also an essential component of BMSC therapy. Conclusively, our data suggested that BMSC transplantation can alleviate spinal injury induced by 2,5-HD through AKT/mTOR/CREB by NGF-dependent and -independent pathways.
Lactylation-mitochondria axis in chronic kidney disease: metabolic reprogramming, epigenetic dysregulation, and therapeutic potential.
Gan Y, Zhang J, Fu X … +7 more , Wang Y, Zhao C, Dai Y, Yan H, Liu Q, Sun W, Liu L
Mol Cell Biochem · 2026 Mar · PMID 41511718 · Publisher ↗
Chronic kidney disease (CKD) is a global public health problem, and its prevalence and mortality are rising rapidly worldwide. At present, CKD treatment can only partially delay the progression of the disease, and it is...
Chronic kidney disease (CKD) is a global public health problem, and its prevalence and mortality are rising rapidly worldwide. At present, CKD treatment can only partially delay the progression of the disease, and it is necessary to explore safer and more effective treatment options. Renal interstitial fibrosis is a common pathological process in CKD. The essence of renal fibrosis is the excessive deposition of extracellular matrix (ECM), tubulointerstitial fibrosis and glomerulosclerosis caused by various injury reactions, which eventually leads to renal parenchymal destruction and loss of renal function. Therefore, anti-renal fibrosis therapy plays a crucial role in delaying the progression of CKD. Unfortunately, the current treatment options to reverse or prevent the progression of renal fibrosis are very limited. Under normal circumstances, proximal renal tubular epithelial cells mainly rely on fatty acid oxidation (FAO) to obtain energy. In renal tubulointerstitial fibrosis, lipid metabolism disorders occur, resulting in a large amount of lipid deposition in the kidney, causing kidney damage. It can be seen that maintaining the level of FAO metabolism is of great significance for maintaining normal renal function.Kidney is one of the key organs of lactic acid metabolism. Under normal circumstances, renal cortex is the main place of lactic acid metabolism and absorption. In the renal cortex, tubular epithelial cells are the main bearers. This process occurs primarily in the glucose-lactate circulation between the cortex and medulla of the kidney, but the ability of tubular epithelial cells to metabolize lactate is impaired under pathological conditions, especially in acute kidney injury and diabetic nephropathy, resulting in lactic acid accumulation and inflammation and mitochondrial dysfunction. Lactic acid accumulation creates new post-translational modifications-lactylation modifications, metabolic reprogramming resulting from lactylation modifications, regulation of gene transcription, protein expression, and cellular metabolism, critical in renal pathology, and lactylation plays a role in inflammatory responses such as mitochondrial dysfunction in AKD. Intervening in the lactase process in kidney disease may lead to new therapeutic strategies.
Single-cell transcriptomic profiling identifies therapeutic subpopulations of adipose-derived mesenchymal stromal cells for human keloid management.
Wang S, Ma F, Bai Z … +5 more , Zhang W, Song X, Zhang J, Han P, Li X
Mol Cell Biochem · 2026 Mar · PMID 41511717 · Publisher ↗
OBJECTIVE: Keloids are pathological scars characterized by excessive collagen deposition that occurs during wound healing after skin injury. Keloid fibroblasts (KF) and keloid keratinocytes (KK) are key contributors to k...
OBJECTIVE: Keloids are pathological scars characterized by excessive collagen deposition that occurs during wound healing after skin injury. Keloid fibroblasts (KF) and keloid keratinocytes (KK) are key contributors to keloid pathogenesis. Although adipose-derived mesenchymal stromal cells (ASCs) have been investigated for keloid therapy, their therapeutic potential and underlying mechanisms require further elucidation. This study aimed to characterize the therapeutic potential of ASCs for human keloid management. METHODS: Molecular profiles associated with keloid pathogenesis were characterized through integrative analyses, including gene expression profiling, functional annotation, protein-protein interaction mapping, and hub gene identification. Single-cell RNA sequencing (scRNA-seq) was used to identify ASC subpopulations with inhibitory effects on keloid development. The therapeutic efficacy of these subpopulations was subsequently assessed in a miniature pig model of hypertrophic scar. RESULTS: Upregulation of hub genes such as NOG and IL6 was strongly associated with KF formation, whereas increased expression of APP and NOTCH1 was implicated in KK development. Functional scRNA-seq analysis identified ASC subpopulations capable of inhibiting the development of KF, KK, or both through molecular interactions with these hub genes. Administration of porcine ASCs enriched in the identified inhibitory subpopulations effectively prevented hypertrophic scar formation in the miniature pig model. CONCLUSION: This study delineated key molecular signatures underlying keloid formation and identified ASC subpopulations with targeted inhibitory activity against pathological cell types involved in keloid development. These findings support the potential application of ASC-based interventions for prophylaxis and treatment of hypertrophic scarring in humans.
SETD2 inhibited T-cell acute lymphocytic leukemia invasion and infiltration by inhibiting the JAK/STAT pathway.
Qiu L, Ren S, Li M … +6 more , Dou B, Chen D, Zhang N, Cai J, Yao H, Fan F
Mol Cell Biochem · 2026 Mar · PMID 41489770 · Publisher ↗
T-cell acute lymphocytic leukemia (T-ALL) is a malignant transformation of immature precursor T-cells that is highly aggressive. The disruption of SETD2 is thought to be a unique epigenetic mechanism for leukemia. This s...
T-cell acute lymphocytic leukemia (T-ALL) is a malignant transformation of immature precursor T-cells that is highly aggressive. The disruption of SETD2 is thought to be a unique epigenetic mechanism for leukemia. This study aimed to investigate the role and possible mechanism of SETD2 in T-ALL. The expression of SETD2 in T-ALL tissues and cells was detected by RT-PCR, and siRNA (si-NC/si-SETD2) and overexpressed plasmids (ov-NC/ov-SETD2) were used to transfected T-ALL cell lines JURKAT and MOLT-4, and cell proliferation, migration/invasion and cell cycle were detected by CCK8, Transwell, flow cytometry, respectively. WB was used to detect the changes in the JAK/STAT pathway. The JAK/STAT inhibitor AG490 was further used to demonstrate the role of JAK/STAT in SETD2 regulation of T-ALL. Then, the effects of SETD2 on T-ALL tissue infiltration were verified in vivo. Results showed that SETD2 was significantly lowly expressed in T-ALL, and si-SETD2 promoted the proliferation, migration, invasion, cell cycle, and activation of the JAK/STAT pathway of T-ALL cells, while overexpression of SETD2 showed the opposite inhibitory effect. The use of AG490 inhibited the promoting effect of si-SETD2 on T-ALL, suggesting that JAK/STAT was involved in the regulation of SETD2 on T-ALL. In vivo experiments further confirmed that silencing SETD2 decreased the body weight of mice and increased the infiltration of JURKAT cells in the liver, kidney, spleen, lung, and brain, while overexpression of SETD2 showed inhibitory effects. In conclusion, SETD2 played an important role in T-ALL by inhibiting the JAK/STAT pathway to inhibit T-ALL proliferation, invasion, and transfection.
ELANE inhibits the progression of osteosarcoma via suppressing the CXCL12/CXCR4 axis.
Zeng H, Wang C, Zhong Y … +1 more , Zeng D
Mol Cell Biochem · 2026 Mar · PMID 41489769 · Publisher ↗
We aimed to screen novel biomarkers for osteosarcoma (OS) using bioinformatics analysis and explore their regulatory mechanisms in OS progression. Differentially expressed genes (DEGs) were screened from GSE36001 and GSE...
We aimed to screen novel biomarkers for osteosarcoma (OS) using bioinformatics analysis and explore their regulatory mechanisms in OS progression. Differentially expressed genes (DEGs) were screened from GSE36001 and GSE19276 datasets. Hub genes were isolated from protein-protein interaction networks and subsequently validated using real-time quantitative polymerase chain reaction, with their expression patterns further confirmed in an independent external cohort (GSE16088 dataset). The role of neutrophil elastase (ELANE) in OS was assessed using immunohistochemical staining of Ki67 and hematoxylin-eosin staining in a subcutaneous tumor experiment. The proliferation, migration, invasion, and apoptosis were determined using Cell Counting Kit-8, wound healing, Transwell, and flow cytometry assays. A total of 71 overlapping DEGs related to OS were identified. ELANE, AZU1, DEFA4, RNASE3, PRTN3, and CTSG were identified as hub genes of OS, which were down-regulated in OS cells. ELANE was selected as the research target. Overexpression of ELANE inhibited tumor growth in OS. In vitro experiment, overexpression of ELANE suppressed the proliferation, migration, and invasion, while promoting apoptosis of OS cells. Conversely, its silencing had the opposite effect. Furthermore, chemokine signaling pathway was selected as the downstream pathway of ELANE in OS. ELANE inhibited the expression of CXCL12 and CXCR4. The activation of CXCL12/CXCR4 axis reversed the inhibitory impact of ELANE on the proliferation, migration, and invasion, as well as the promoting effects of ELANE on apoptosis of OS cells. ELANE was a novel gene signature of OC, which exerts an anti-tumor effect on OS progression via inhibiting CXCL12/CXCR4 axis.
HSP72-AMPK axis mitigates hypoxia-induced cellular senescence to promote colorectal cancer development.
Liu G, Wang X, Yang X … +6 more , Wu J, Li Y, Lu Y, Shang A, Chen C, Sun R
Mol Cell Biochem · 2026 Feb · PMID 41483125 · Publisher ↗
Colorectal cancer (CRC) remains a major global health challenge, with steadily increasing incidence and mortality. Current diagnostic biomarkers exhibit limited clinical utility due to insufficient sensitivity and specif...
Colorectal cancer (CRC) remains a major global health challenge, with steadily increasing incidence and mortality. Current diagnostic biomarkers exhibit limited clinical utility due to insufficient sensitivity and specificity. While cellular senescence promotes CRC development through chronic inflammation and senescence-associated secretory phenotype (SASP), and hypoxia paradoxically drives malignant progression in tumors despite suppressing growth in normal tissues, the underlying mechanisms connecting these pathways remain incompletely understood. This study reveals that heat shock protein 72 (HSP72) orchestrates CRC progression under hypoxic conditions through a hypoxia-inducible factor 1 α (HIF1α)–HSP72–AMPK positive feedback loop. Specifically, hypoxia stabilizes HIF1α, enabling its specific binding to the 1207 bp region of the HSP72 promoter and subsequent transcriptional upregulation. Then, HSP72 regulates AMPK pathway activation, forming a signaling hub that maintains HIF1α stability and thereby couples metabolic reprogramming with sustained tumor proliferation. This circuit further enables senescence evasion by suppressing SA-β-Gal activity, blocking SASP factor secretion, and enhancing anti-apoptotic pathways. Clinical translation demonstrates that circulating HSP72 serves as both an early diagnostic biomarker and an independent predictor of metastatic risk. Collectively, our findings establish HSP72 with dual significance—as a promising molecular marker for non-invasive early detection and as a theoretical foundation for targeting the HSP72-AMPK pathway and disrupting the HIF1α–HSP72 axis, offering novel strategies against hypoxia-adapted and therapy-resistant CRC.
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