Mol. Cell. Biochem. [JOURNAL]
Sun
200 papers
Network pharmacology and experimental verification to explore the therapeutic mechanism of esketamine in postoperative cognitive dysfunction.
Zhan Y, Liu S, Li Y … +1 more , Qi S
Mol Cell Biochem · 2026 Jun · PMID 42334522 · Publisher ↗
Postoperative Cognitive Dysfunction (POCD) is one of the most common perioperative complications, which has already become a significant challenge for postoperative patient management. Esketamine has demonstrated promisi...
Postoperative Cognitive Dysfunction (POCD) is one of the most common perioperative complications, which has already become a significant challenge for postoperative patient management. Esketamine has demonstrated promising therapeutic potential for POCD; however, its specific mechanism remains incompletely understood. This study aimed to investigate the mechanism of esketamine in treating POCD by integrating network pharmacology, in vivo experiments, and in vitro experiments. In this study, network pharmacology combined with experimental validation was employed to explore the underlying mechanisms by which esketamine ameliorates POCD. Initially, the key targets and pathways were analyzed using network pharmacology. Behavioral tests were performed to evaluate postoperative motor and cognitive function in mice. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of inflammatory factors. Western blotting was applied to measure the expression of proteins related to signaling pathways, and immunofluorescence staining was conducted to assess microglial activation. A total of 41 potential targets and 56 signaling pathways were identified for POCD intervention using network pharmacology analysis. In vivo experiments showed that esketamine improved postoperative memory and cognitive function in mice, reduced neuroinflammatory responses in the hippocampus, and inhibited microglial M1 polarization. Further experiments revealed that this protective effect was mediated by regulation of the PI3K/AKT/GSK3β signaling pathway. This study demonstrates that the anti-neuroinflammatory effect of esketamine in POCD is mediated by its activation of the PI3K-AKT-GSK3β pathway, which suppresses excessive microglial activation.
Pharmacological effect of rhCC16 on COPD: anti-senescence via the PI3K-AKT-mTOR pathway.
Gao R, Wu S, Zhang CL … +6 more , Liu CF, Li T, Guo M, Chen ZY, Wang HL, Pang M
Mol Cell Biochem · 2026 Jun · PMID 42322521 · Publisher ↗
Cigarette smoke (CS) is a major risk factor for chronic obstructive pulmonary disease (COPD). CS exposure disrupts the oxidant‑antioxidant balance in the lungs, which may contribute to cellular senescence - a process imp...
Cigarette smoke (CS) is a major risk factor for chronic obstructive pulmonary disease (COPD). CS exposure disrupts the oxidant‑antioxidant balance in the lungs, which may contribute to cellular senescence - a process implicated in the initiation and progression of COPD. Club cell secretory protein 16 (CC16) is produced by the airway epithelium, and reduced CC16 levels have been associated with COPD pathogenesis. In this study, we investigated the potential anti‑senescence effect of recombinant human CC16 (rhCC16) using both in vitro and in vivo models and explored the underlying mechanisms. A cellular senescence model was established by exposing A549 type II alveolar epithelial cells to cigarette smoke extract (CSE). Senescence markers were assessed in the presence or absence of rhCC16 treatment. A mouse model of COPD was generated by chronic CS exposure, and rhCC16 was administered intranasally. Senescence markers in lung tissues were evaluated by immunohistochemistry. Our results indicate that the protective effect of rhCC16 is associated with inhibition of the PI3K‑AKT‑mTOR pathway and restoration of autophagic flux. Furthermore, the anti‑senescence action of rhCC16 in A549 cells may involve integrin α4β1 and clathrin‑mediated endocytosis. In the CS‑exposed mouse model, rhCC16 treatment improved pulmonary function and attenuated lung pathological injury. Collectively, these findings suggest that rhCC16 alleviates CS‑induced cellular senescence through modulation of the PI3K‑AKT‑mTOR/autophagy axis, and may therefore represent a potential candidate for senescence‑targeted therapy in COPD.
Correction to: Puerarin alleviates myocardial ischemia-reperfusion injury by enhancing FUNDC1-mediated mitophagy.
Feng N, Zhang A, Yao L … +11 more , Tang J, Lu M, Shi D, Zhu Z, Liu R, Chen J, Min X, Yang H, Xu H, Zhang W, He X
Mol Cell Biochem · 2026 Jun · PMID 42319716 · Publisher ↗
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CCL3 promotes oxaliplatin resistance in gastric cancer via CCR5-mediated tumor cell survival and macrophage M2 polarization.
Cheng X, Qin Z
Mol Cell Biochem · 2026 Jun · PMID 42319715 · Publisher ↗
Although oxaliplatin (Oxa)-based chemotherapy is a standard treatment for gastric cancer (GC), its clinical efficacy is frequently limited by the development of Oxa resistance. Chemokine CCL3 is linked to tumor growth, w...
Although oxaliplatin (Oxa)-based chemotherapy is a standard treatment for gastric cancer (GC), its clinical efficacy is frequently limited by the development of Oxa resistance. Chemokine CCL3 is linked to tumor growth, which can result in tumor-immune interactions and treatment resistance. This work examined the function of CCL3 in Oxa resistance in macrophages, patient-derived organoids (PDO), and GC cells. Differential expression, weighted gene co-expression network analysis (WGCNA), PPI network, and ROC analysis were performed on the GSE128967 dataset. Oxa-resistant GC cell lines (MKN45/Oxa, SGC7901/Oxa) and PDOs were used to evaluate the function of CCL3 by siRNA knockdown and overexpression. To evaluate CCL3-driven macrophage polarization and its effect on Oxa sensitivity, THP-1-derived macrophages were co-cultured with GC cells. Cell viability, migration/invasion, and expression of CCL3, CCR1/CCR5, and M1/M2 markers were examined by Transwell assays, qRT-PCR, CCK-8, and Western blot. WGCNA highlighted an FOLFOX-related yellow module, from which CCL3 emerged as a hub gene with the highest prognostic accuracy. CCL3 was upregulated in Oxa-resistant GC cells and PDOs. CCL3 knockdown reduced cell migration, invasion, and PDO formation under Oxa treatment, whereas overexpression enhanced resistance. CCL3-overexpressing GC cells promoted M2 polarization of co-cultured macrophages, which in turn further increased Oxa resistance in GC cells. Mechanistically, CCR5 mediated CCL3-induced chemoresistance and macrophage M2 polarization. The CCL3/CCR5 axis drives Oxa resistance in GC by boosting tumor cell survival and fostering immunosuppressive M2 macrophages. Targeting this pathway may offer a strategy to overcome chemoresistance in GC.
Deciphering the interplay between cuproptosis and mitochondrial energy metabolism in thyroid cancer: a multi-omics study for molecular subtyping, prognosis, and tumor microenvironment characterization.
Le H, Wu Y, Wu N … +5 more , Jing R, Zhou X, Li Y, Yi S, Zhang H
Mol Cell Biochem · 2026 Jun · PMID 42319714 · Publisher ↗
Thyroid cancer (THCA) exhibits substantial heterogeneity in clinical outcomes. The interaction between cuproptosis, a novel copper-dependent form of cell death, and mitochondrial energy metabolism, a key regulator of cel...
Thyroid cancer (THCA) exhibits substantial heterogeneity in clinical outcomes. The interaction between cuproptosis, a novel copper-dependent form of cell death, and mitochondrial energy metabolism, a key regulator of cellular bioenergetics, may influence tumor behavior, yet its role in THCA is not fully elucidated. We integrated transcriptomic data from The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA, n = 510; 457 with survival information) and Gene Expression Omnibus (GEO) cohorts (n = 101). Genes related to cuproptosis and mitochondrial energy metabolism (CMEMRGs) were systematically identified. Bioinformatic analyses included consensus clustering, immune cell deconvolution (CIBERSORT, ESTIMATE), prognostic model construction (LASSO Cox regression), and pathway enrichment (GSEA). We identified a landscape of 460 CMEMRGs in THCA. Unsupervised consensus clustering based on prognostic CMEMRGs revealed two molecular subtypes (Subtype A, n = 393; Subtype B, n = 117) with distinct survival outcomes (p < 0.001). Subtype B was associated with an immune-enriched microenvironment, characterized by differential infiltration of lymphocytes including CD8 + T cells and naïve B cells, and exhibited lower Tumor Immune Dysfunction and Exclusion (TIDE) scores, suggesting a potentially more favorable response to immunotherapy. A prognostic signature comprising 15 CMEMRGs was refined to a 3-gene model (APOE, PRR15, and C3) using LASSO regression. This simplified signature demonstrated predictive value for 4-, 5-, and 6-year overall survival (area under the curve [AUC] = 0.853, 0.789, and 0.789, respectively). Patients stratified into high-risk groups by this model exhibited elevated stromal and immune scores. The risk score showed a trend toward independent prognostic value in multivariate analysis, though further validation is needed. Gene Set Enrichment Analysis (GSEA) indicated an association with MAPK signaling pathways, and protein-protein interaction analysis suggested a direct link between APOE and C3. This integrative analysis indicates that the cuproptosis-mitochondrial energy metabolism axis could be implicated in THCA heterogeneity. The identified molecular subtypes and the 3-gene prognostic signature could provide supplementary insights for risk stratification and warrant further investigation into personalized therapeutic strategies.
Effects of LATS1/2 kinases inhibition on lung epithelial cells in a regeneration model.
Govorova IA, Novikova YA, Sutyagina OI … +5 more , Nikitochkina SY, Sabirov MS, Starinnov ZR, Volozhinskaia AA, Vorotelyak EA
Mol Cell Biochem · 2026 Jun · PMID 42319713 · Publisher ↗
Research focused on studying Hippo signaling up- and downregulation in a model of mouse lung cell regeneration. The cell-specific role of the activation and inhibition of Hippo signaling is demonstrated at the cellular l...
Research focused on studying Hippo signaling up- and downregulation in a model of mouse lung cell regeneration. The cell-specific role of the activation and inhibition of Hippo signaling is demonstrated at the cellular level within the context of a unified bronchoalveolar lung organoid model. We used pharmacological modulators of Hippo pathway components-TRULI and verteporfin. The findings revealed that inhibition of Lats1/2 kinases via TRULI leads to different levels of Hippo gene expression for different lung cell types. The inhibition of Lats1/2 kinases enhances cell proliferation in the bronchiolar epithelium, while verteporfin suppresses it. However, no changes in the cellular composition of the bronchiolar epithelium (except ciliated cells) were observed with either TRULI or verteporfin. Inhibition of Lats1/2 kinases in the alveolar epithelium leads to a decrease in type 2 alveolocytes and alters their differentiation trajectories. The results demonstrate a cell-specific influence of Hippo modulation on the lung cells and may prove useful for the development of novel therapeutic approaches for the treatment of respiratory pathologies.
COLEC12 promotes pancreatic cancer progression via the activation of the TGF-β signaling pathway.
Feng X, Xu J, Yang Q … +3 more , Ren Y, Chen H, Jiang Z
Mol Cell Biochem · 2026 Jun · PMID 42319712 · Publisher ↗
Collectin Subfamily Member 12 (COLEC12), a C-type lectin family member with collagen-like and carbohydrate recognition domains, remains poorly characterized in pancreatic cancer (PC). COLEC12 expression was analyzed by b...
Collectin Subfamily Member 12 (COLEC12), a C-type lectin family member with collagen-like and carbohydrate recognition domains, remains poorly characterized in pancreatic cancer (PC). COLEC12 expression was analyzed by bioinformatics and immunohistochemistry. Functional assays (CCK-8, colony formation, EdU, flow cytometry, Transwell) and a xenograft model were used to assess its tumor-promoting effects. Mechanistically, transcriptome sequencing, Western blotting, co-immunoprecipitation (Co-IP), molecular docking, truncation mutant mapping, cycloheximide (CHX) chase assay, and ubiquitination assays were performed. The Cancer Genome Atlas (TCGA) data were used for immune infiltration analysis, and quantitative real-time PCR (qRT-PCR) was used to examine the role of COLEC12 in macrophage polarization. Chemosensitivity to gemcitabine and 5-fluorouracil (5-FU) was also evaluated. COLEC12 was upregulated in PC and promoted cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while suppressing apoptosis. Mechanistically, COLEC12 directly bound to TGF-β1 via its collagen-like domain, as demonstrated using truncation mutants. CHX chase assays revealed that COLEC12 overexpression delayed TGF-β1 degradation, and ubiquitination assays showed that COLEC12 knockdown increased TGF-β1 ubiquitination, indicating that COLEC12 stabilizes TGF-β1 by suppressing its ubiquitin-proteasome degradation, thereby sustaining activation of the TGF-β/Smad pathway. Furthermore, COLEC12 expression positively correlated with immune cell infiltration levels in TCGA data, and qRT-PCR revealed that COLEC12 expression in PC cells promotes M2 polarization of co-cultured macrophages. Knockdown of COLEC12 increased the sensitivity of PC cells to gemcitabine and 5‑FU. This study reveals, for the first time, the tumor-promoting function of COLEC12 in PC and highlights its potential as a therapeutic target in PC.
Therapeutic effects of alprostadil on CCl-induced hepatic fibrosis in rats and investigation of its molecular mechanisms.
Shen Z, Zhang Y, Zhao R … +7 more , Yang X, Guo J, Dong M, Ma T, Ma S, Sai N, Dong Z
Mol Cell Biochem · 2026 Jun · PMID 42307830 · Publisher ↗
Hepatic fibrosis (HF) is driven by hepatic stellate cell (HSC) activation. Although cyclic adenosine monophosphate (cAMP) is a key antifibrotic signal, whether pharmacological cAMP elevation acts through protein kinase A...
Hepatic fibrosis (HF) is driven by hepatic stellate cell (HSC) activation. Although cyclic adenosine monophosphate (cAMP) is a key antifibrotic signal, whether pharmacological cAMP elevation acts through protein kinase A (PKA) or exchange protein directly activated by cAMP 1 (EPAC1) remains unclear. Alprostadil (PGE1) elevates intracellular cAMP, but its antifibrotic mechanism is undefined. Using CCl₄-induced HF in rats and primary HSCs, we found that Alprostadil markedly reduced liver injury, collagen deposition, and HSC activation. Fibrotic livers showed increased total cAMP but decreased PKA- and EPAC1-bound cAMP, indicating depletion of functional cAMP microdomains. Alprostadil restored effector-bound cAMP, increased EPAC1 expression, and enhanced PKA/CREB phosphorylation. Notably, EPAC1 inhibition-but not PKA inhibition-attenuated the antifibrotic effects of Alprostadil in vivo and in vitro. These findings identify EPAC1 as the dominant downstream effector through which Alprostadil restores localized cAMP signaling to suppress HSC activation and hepatic fibrosis.
Olfactory bulb 6-OHDA neurotoxicity as a model of early cortical dysfunction.
Fiorenza-Neto E, Gattiboni BB, Almeida K … +12 more , Marqueze LF, Mogharbel BF, de Aguiar JRN, Marques LC, Lazarini LR, Carvalhal SRS, Boldt A, Cunha RC, Carvalho KAT, Thirupathi A, Radak Z, Pinho RA
Mol Cell Biochem · 2026 Jun · PMID 42301540 · Publisher ↗
The olfactory bulb (OB) is one of the earliest brain regions affected in neurodegenerative diseases such as Parkinson's disease (PD). Its high metabolic rate, dopaminergic modulation, and connectivity with the cortical a...
The olfactory bulb (OB) is one of the earliest brain regions affected in neurodegenerative diseases such as Parkinson's disease (PD). Its high metabolic rate, dopaminergic modulation, and connectivity with the cortical and limbic regions make it particularly vulnerable to early neuroinflammatory and oxidative processes. This study aimed to investigate whether the administration of 6-hydroxydopamine (6-OHDA) into the OB induces behavioral, redox, and inflammatory alterations associated with early cortical disturbances. Male Wistar rats were randomly assigned to the sham or 6-OHDA groups and underwent stereotaxic injection of the vehicle or 6-OHDA into the left OB. Behavioral performance was assessed in the open-field test 12 days after surgery, and cortical tissue was collected for biochemical and molecular analyses. Cytokines (IL-1β, IL-6, TNF-α, IL-10, IFN-γ, and MCP-1) were quantified by Luminex, redox parameters (CAT, GPx, MDA, and protein carbonyls) by spectrophotometry, and neuronal signaling proteins (c-FOS, CREB, and BDNF) by qPCR. Animals with 6-OHDA lesions exhibited decreased latency and increased time spent in the central zone of the open field, indicating altered exploratory behavior. IL-6 levels were significantly elevated, whereas IFN-γ was reduced in the cortex, while IL-1β, TNF-α, MCP-1, and IL-10 remained unchanged. The oxidative stress markers MDA and protein carbonyls were increased, while catalase and glutathione peroxidase activities showed no change. The expression of c-FOS, CREB, and BDNF was not significantly modified. These findings indicate that localized 6-OHDA administration in the OB is sufficient to elicit behavioral, inflammatory, and oxidative alterations in connected cortical regions, which may resemble early non-motor features associated with olfactory dysfunction, without representing a neurodegenerative disease-specific process.
Serum miR-197-3p as a diagnostic and prognostic biomarker in traumatic brain injury: involvement in MyD88-dependent microglial polarization.
Xu Y, Tian Y, Wang L … +1 more , Du Z
Mol Cell Biochem · 2026 Jun · PMID 42274834 · Publisher ↗
The prognosis and management of severe traumatic brain injury (TBI) remain significant clinical challenges. The role of serum miR-197-3p in TBI remains unclear. This study aimed to explore its potential as a diagnostic a...
The prognosis and management of severe traumatic brain injury (TBI) remain significant clinical challenges. The role of serum miR-197-3p in TBI remains unclear. This study aimed to explore its potential as a diagnostic and prognostic biomarker and to elucidate its pathophysiological mechanism. A total of 206 participants were enrolled, including 66 healthy controls, 72 patients with mild-to-moderate TBI, and 68 patients with severe TBI. Serum miR-197-3p expression was measured by qRT-PCR. Its prognostic factors were analyzed via Cox regression models. An oxygen-glucose deprivation (OGD) model was established using the murine microglial BV2 cell line. The regulatory effect of miR-197-3p on microglial polarization was validated by Western blotting and ELISA. Serum levels of miR-197-3p were lowest in patients with severe TBI. The area under the ROC curve for distinguishing severe from mild-to-moderate TBI was 0.872. Low miR-197-3p expression was a potential indicator of poor 6-month functional outcomes in severe TBI patients. miR-197-3p directly targeted the 3'UTR of MyD88 mRNA and inhibited its expression. In the OGD model, overexpression of miR-197-3p suppressed microglial polarization toward the pro-inflammatory (M1) phenotype while promoting a shift toward the anti-inflammatory/reparative (M2) phenotype. This effect was reversed by concurrent overexpression of MyD88. Serum miR-197-3p is a promising candidate biomarker for TBI, showing potential for auxiliary injury severity stratification and as an independent predictor of poor prognosis. Its mechanism may involve modulating neuroinflammation by targeting MyD88 and regulating microglial polarization, warranting further investigation.
Alginate oligosaccharides promote wound healing and induce macrophage M2 polarisation by activating the PI3K/AKT1 signalling pathway.
Liu L, Pan B, Tao Z … +3 more , Zhu S, Liu Q, Jin J
Mol Cell Biochem · 2026 Jun · PMID 42274833 · Publisher ↗
The objective of this study was to investigate the effects of alginate oligosaccharides on wound cell proliferation, migration, apoptosis, macrophage polarisation, and wound healing. The results of the Cell Counting Kit-...
The objective of this study was to investigate the effects of alginate oligosaccharides on wound cell proliferation, migration, apoptosis, macrophage polarisation, and wound healing. The results of the Cell Counting Kit-8, Transwell method, and caspase-3 immunofluorescence showed that alginate oligosaccharides effectively promoted keratinocyte proliferation, migration, and reduced apoptosis by activating the PI3K/AKT1 signalling pathway. The polarisation of macrophages was detected using iNOS and Arg-1 immunofluorescence. Alginate oligosaccharides induced M2 polarisation. This was negated after using an AKT1 inhibitor. In vitro cell experiments showed that alginate oligosaccharides did not affect macrophage proliferation but showed a significant reduction in macrophage numbers in in vivo animal wound models, accompanied by a trend in M2 polarisation. Although AOs had no direct in vitro antibacterial effect, their in vivo application modulated the composition of wound microbiota, which may be related to AOs induced macrophage M2 polarization and the improvement of local inflammatory response. The combined effects of alginate oligosaccharides on keratinocytes and macrophages ultimately promoted wound healing and altered microbiota composition, thereby providing a new, potential treatment option for wound healing(Fig. 1).
Dysregulated KIF2A correlates with p53 expression pattern in breast cancer.
Hao Y, Ma SQ, Xu T … +4 more , Wu JQ, Ma R, Wang YW, Wang JL
Mol Cell Biochem · 2026 Jun · PMID 42257979 · Publisher ↗
Kinesin family member 2A (KIF2A) and p53 play crucial roles in tumor development and progression. However, their correlation in breast cancer remains unclear. Immunohistochemistry (IHC) was performed on 357 breast cancer...
Kinesin family member 2A (KIF2A) and p53 play crucial roles in tumor development and progression. However, their correlation in breast cancer remains unclear. Immunohistochemistry (IHC) was performed on 357 breast cancer specimens to investigate the expression status of KIF2A and p53, their correlations with clinicopathological parameters and prognosis, and their interrelationship in breast cancer. The results demonstrated that KIF2A was highly expressed in breast cancer tissues and exhibited two subcellular localization patterns: nuclear-enriched and cytoplasmic-enriched localization. High KIF2A expression was associated with the human epidermal growth factor receptor 2 (HER2)-positive subtype, lymph node metastasis (LNM), high Ki67 index, and advanced TNM stage, whereas cytoplasmic-enriched localization was associated with higher tumor grade. Both high KIF2A expression and cytoplasmic-enriched localization predicted poor prognosis in patients with breast cancer. A composite index integrating KIF2A expression and localization was an independent prognostic factor. p53 IHC analysis revealed expression pattern categorized as wild-type (57.7%), overexpression (20.4%), and null pattern (21.8%). Abnormal p53 expression (overexpression and null pattern) was associated with LNM, advanced N-stage, high histological grade, estrogen receptor-negative status, progesterone receptor-negative status, HER2-positive status, high Ki67 index, and triple-negative molecular subtypes. Patients with the wild-type, null, and overexpression pattern demonstrated progressively worse prognosis. Additionally, the combined status of KIF2A and p53 IHC could effectively stratify the prognosis of breast cancer. Finally, KIF2A expression was found to be higher in patients with abnormal p53 expression. This study revealed the expression interplay and clinical significance of KIF2A and p53 in breast cancer. The identified association between KIF2A and p53 may provide insights for future research on their roles in breast cancer.
Enhanced ITGA3 expression induced by helicobacter pylori infection facilitates gastric cancer progression via NF-κB and Smad4.
Xing Y, Chu Y, Zhu W … +4 more , Jing F, Ma X, Wang Y, Jia Y
Mol Cell Biochem · 2026 Jun · PMID 42240927 · Publisher ↗
Helicobacter pylori (H. pylori) infection is a key risk factor in the onset and progression of gastric cancer (GC). The integrin subunit alpha 3 (ITGA3) is frequently upregulated in various malignancies and may influence...
Helicobacter pylori (H. pylori) infection is a key risk factor in the onset and progression of gastric cancer (GC). The integrin subunit alpha 3 (ITGA3) is frequently upregulated in various malignancies and may influence cell proliferation and metastasis under specific conditions. However, the mechanisms that govern ITGA3 activation and its role in the inflammation-driven transformation of GC remain poorly understood. This study explores the impact of ITGA3 in response to H. pylori infection and its involvement in gastric tumorigenesis. Elevated ITGA3 expression was observed in gastric tissues and in GC cells exposed to H. pylori, and was associated with enhanced malignant phenotypes in vitro and increased tumor growth in vivo. Mechanistically, ITGA3 appears to promote GC progression, at least in part, through activation of the NF-κB/mTOR signaling axis and enhancement of TGF-β-related signaling, thereby contributing to tumor proliferation, epithelial-mesenchymal transition (EMT), and migration. Additionally, H. pylori infection led to an increase in p-STAT3 expression, which transcriptionally upregulates ITGA3, thereby further enhancing its pro-tumorigenic effects. This study suggests a previously underappreciated role for ITGA3 in H. pylori-associated GC. H. pylori infection induces p-STAT3 activation, driving ITGA3 expression at the transcriptional level. In turn, ITGA3 promotes GC progression by concurrently activating the NF-κB/mTOR and TGF-β signaling pathways, facilitating tumor cell proliferation, EMT, and migration, and thereby accelerating the malignancy of GC. These findings suggest that the ITGA3/NF-κB/mTOR/TGF-β axis may represent a potential therapeutic target for H. pylori-positive GC.
Editorial Expression of Concern: Chloride channels and mast cell function: pioneering new frontiers in IBD therapy.
Aljameeli AM, Alsuwayt B, Bharati D … +4 more , Gohri V, Mohite P, Singh S, Chidrawar V
Mol Cell Biochem · 2026 Jun · PMID 42234384 · Publisher ↗
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Retraction Note: Knockdown of TRAP1 promotes cisplatin-induced apoptosis by promoting the ROS-dependent mitochondrial dysfunction in lung cancer cells.
Zhang X, Dong Y, Gao M … +4 more , Hao M, Ren H, Guo L, Guo H
Mol Cell Biochem · 2026 Jun · PMID 42234383 · Publisher ↗
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MELK inhibits cuproptosis in diffuse large B-cell lymphoma cells via the PI3K/mTOR/S6K-DLAT signaling axis.
Wang X, Wang C, Wang C … +5 more , Li M, Ye W, Shi M, Hou Y, Ding M
Mol Cell Biochem · 2026 Jun · PMID 42228272 · Publisher ↗
With a wide range of genetic characteristics and metabolic requirements, diffuse large B-cell lymphoma (DLBCL) is an extremely complex cancer. Although maternal embryonic leucine zipper kinase (MELK) has been linked to t...
With a wide range of genetic characteristics and metabolic requirements, diffuse large B-cell lymphoma (DLBCL) is an extremely complex cancer. Although maternal embryonic leucine zipper kinase (MELK) has been linked to the development of tumors, its function in DLBCL and control of cuproptosis, a copper-dependent mechanism of cell deathproduce, is yet unknown. Hub genes in DLBCL were found using integrated bioinformatic analysis of the TCGA and GEO datasets. Using qRT-PCR, WB, cell viability, Transwell, and mitochondrial assays, MELK expression was examined in DLBCL cell lines (OCI-LY8, U2932, OCI-LY7) and normal B cells (GM12878). Functional analyses were conducted in selected DLBCL cell lines (OCI-LY7 and OCI-LY8) to accurately assess the biological roles of MELK. Elesclomol (15 nM) and copper chloride (CuCl₂, 10 µM) were used to induce cuproptosis, while DLAT overexpression and S6 kinase inhibition were used to clarify signaling processes. MELK expression was considerably elevated in DLBCL tissues and cell lines (P < 0.05). In addition to inducing mitochondrial malfunction, increasing reactive oxygen species, lowering the NADH/NAD⁺ ratio, and triggering intrinsic apoptosis, MELK silencing inhibited proliferation, migration, and invasion. MELK knockdown enhanced the sensitivity of cells to elesclomol-Cu treatment, which in turn induced cuproptosis and further reduced MELK expression. Mechanistically, MELK overexpression increased cell survival, elevated dihydrolipoamide S-acetyltransferase (DLAT), and triggered the PI3K/mTOR/S6K signaling pathway. On the other hand, MELK-mediated effects on cuproptosis and intracellular copper buildup were abolished by S6K suppression or DLAT overexpression. Through the PI3K/mTOR/S6K-DLAT axis, MELK imparts resistance to cuproptosis and increases DLBCL cell survival. MELK targeting may increase copper-induced cytotoxicity, offering a possible DLBCL treatment approach.
Anemoside B4 inhibits mitochondrial dysfunction-related mitophagy in asthma by regulating KAT2B/IRF3 axis.
Tang H, Li P, Shang M … +3 more , Zhou Z, Yang X, Liu B
Mol Cell Biochem · 2026 Jun · PMID 42228271 · Publisher ↗
Asthma is a classical inflammation-related disease, and its pathogenesis is closely associated with mitochondrial dysfunction and mitophagy. Although Anemoside B4 (AmB4) exhibits anti‑inflammatory properties in various d...
Asthma is a classical inflammation-related disease, and its pathogenesis is closely associated with mitochondrial dysfunction and mitophagy. Although Anemoside B4 (AmB4) exhibits anti‑inflammatory properties in various diseases, its role in regulating mitochondrial dysfunction-related mitophagy in asthma remains unknown. In vivo and in vitro asthma models were constructed using house dust mite (HDM)-stimulated BALB/c mice and HDM-treated BEAS-2B cells. Hematoxylin and eosin and periodic acid-Schiff staining were used for the pathological examination of lung tissues. Mitophagy-related proteins were assessed by Western blotting and immunofluorescence. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels were measured using JC-1 and DCFH‑DA assays, respectively. Mitochondria was observed by transmission electron microscopy. Cytokine concentrations were determined by ELISA. The mito‑Keima reporter was employed to directly quantify mitophagy and analyzed by flow cytometry. The effect of KAT2B on IRF3 protein stability was determined by cycloheximide chase assay. The ubiquitination of IRF3 was assessed by immunoprecipitation. Intermolecular interactions were analyzed using co-immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays. The results illuminated AmB4 alleviated asthma by downregulating KAT2B expression, thereby ameliorating mitochondrial dysfunction and suppressing mitophagy in vivo. Furthermore, AmB4 increased the MMP of BEAS-2B cells and reduced levels of ROS, LC3B, and Tomm20 via KAT2B inhibition. Mechanistically, KAT2B promoted the lysine acetylation of interferon regulatory factor 3 (IRF3) at K315, and IRF3 enhanced PTEN-induced putative kinase 1 (PINK1) expression by binding to its promoter. Additionally, AmB4 inhibited mitochondrial dysfunction-related mitophagy by targeting the KAT2B/IRF3/PINK1 axis, thereby alleviating asthma. Specifically, AmB4 suppressed IRF3-mediated PINK1 transcription by inhibiting KAT2B-dependent acetylation of IRF3 at K315, thereby ameliorating mitochondrial dysfunction and suppressing mitophagy, which ultimately improved asthma symptoms.
A spatial transit-retention axis reveals adaptive immune organisation in psoriatic disease.
Bonilha CS
Mol Cell Biochem · 2026 Jun · PMID 42228270 · Publisher ↗
Spatial organisation of immune cells reflects a balance between tissue anchoring and migratory compatibility, yet how this balance is structured within inflammatory skin disease remains poorly understood. Spatial transcr...
Spatial organisation of immune cells reflects a balance between tissue anchoring and migratory compatibility, yet how this balance is structured within inflammatory skin disease remains poorly understood. Spatial transcriptomic analyses defined transit-retention immune organisation across lesional and non-lesional skin in atopic dermatitis (AD) and psoriasis (PsO). A unified transit-retention axis captured contextual immune organisation within leukocyte-rich tissue microenvironments. Non-lesional skin in both diseases exhibited retention-dominant organisation. In contrast, psoriatic lesions showed disruption of retention dominance, accompanied by coordinated alignment of antigen presentation, T cell activation, Th17, and B cell programmes with transit-compatible organisation, a pattern not observed in AD. An independent spatial transcriptomic dataset of psoriatic skin enabled assessment of compartmental specificity and clinical relevance. These analyses identified the epidermis as the primary site of transit-skewed reorganisation, with epidermal transit alignment scaling with disease severity. Extension of the same transcriptional framework to circulating adaptive immune cells using CITE-seq revealed lineage-specific transit-associated features in psoriatic disease. Circulating CD4 T cells and B cells showed stronger transcriptional and protein-level alignment with transit-associated states in PsO and psoriatic arthritis. Together, these analyses reveal transit-skewed adaptive immune organisation as a unifying feature of psoriatic disease.
The role of mitochondrial regulation in macrophage polarization by Ganoderma lucidum polysaccharide for the treatment of colitis-associated colorectal cancer.
Ouyang Z, Ye W, Wen G … +5 more , Li S, Wei T, Chen M, Cai B, Liu H
Mol Cell Biochem · 2026 Jun · PMID 42228269 · Publisher ↗
Colorectal cancer (CRC) is a common malignant tumor of the digestive tract. Ganoderma lucidum polysaccharide (GLP) has shown significant potential in regulating macrophage polarization and treating CRC. However, the role...
Colorectal cancer (CRC) is a common malignant tumor of the digestive tract. Ganoderma lucidum polysaccharide (GLP) has shown significant potential in regulating macrophage polarization and treating CRC. However, the role of mitochondrial regulation in GLP-mediated macrophage polarization in azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated CRC remains unclear. Therefore, we performed cellular and animal experiments to explore how GLP influences mitochondrial dynamics and function, macrophage polarization, and exerts its therapeutic effect against AOM/DSS-induced colitis-associated CRC. The results showed that Mdivi-1 attenuated GLP-induced changes in mitochondrial dynamics and function, further reduced the M1/M2 macrophage ratio. In vivo experiments confirmed that GLP modulates mitochondrial function, promotes M1 macrophage polarization, and thereby inhibits CRC progression without significant side effects. This study provides new insights into the role of mitochondrial modulation in GLP-mediated macrophage polarization and suggests a potential therapeutic avenue for colitis-associated CRC treatment.
Nobiletin attenuates self-renewal in cervical cancer cells and spheres through miR-342-3p upregulation and FOXM1 downregulation.
Huang L, Feng W, Long W … +3 more , Liu H, Li E, Ning Y
Mol Cell Biochem · 2026 Jun · PMID 42228268 · Publisher ↗
Cervical cancer (CC) cells exhibiting self-renewal properties are regarded as the primary drivers of recurrence. Nobiletin (NOB), a polymethoxy flavonoid derived from citrus, demonstrates effective suppression of cancer...
Cervical cancer (CC) cells exhibiting self-renewal properties are regarded as the primary drivers of recurrence. Nobiletin (NOB), a polymethoxy flavonoid derived from citrus, demonstrates effective suppression of cancer stem cell characteristics through the regulation of multiple targets, including key signaling pathways and epigenetic mechanisms. This investigation seeks to evaluate the influence of NOB on self-renewal capabilities and to identify potential epigenetic mechanisms using spheroids derived from HeLa and SiHa cell lines as models for cancer stem-like cells (CCSLCs). The experimental findings demonstrated that NOB markedly diminished self-renewal capabilities, evidenced by reduced sphere formation and decreased protein expression of CD133, CD49f, Oct4, and Sox2 as well as in vivo tumor growth within CCSLCs. Analysis through quantitative polymerase chain reaction indicated NOB elevated miR-342-3p levels while suppressing FOXM1, its target gene expression. Luciferase-based experiments verified miR-342-3p's direct targeting of FOXM1 in CCSLCs obtained from NOB-treated HeLa cells. The alterations in miR-342-3p expression levels, whether through enhancement or suppression, showed corresponding changes in NOB's effectiveness. Moreover, alterations in FOXM1 expression, either via overexpression or knockdown, did not alter NOB-induced miR-342-3p levels but markedly impacted NOB's suppression of self-renewal in both HeLa cells and derived CCSLCs. Thus, NOB inhibits self-renewal by enhancing miR-342-3p levels and diminishing FOXM1 levels in CC cells and derived CCSLCs.
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