Molecular And Cellular Biochemistry[JOURNAL]
Sun
200 papers
CHI3L1: a novel regulator of vascular remodeling in pulmonary arterial hypertension.
Gao S, Zhao S, Wang Y … +5 more , Liu Y, Zhong H, Luo L, Zhu D, Pan S
Mol Cell Biochem · 2026 May · PMID 41910909 · Publisher ↗
Pulmonary arterial hypertension (PAH) is a life-threatening disease. It is characterized by a progressive increase in pulmonary vascular resistance, which leads to pulmonary vascular remodeling. This process involves the...
Pulmonary arterial hypertension (PAH) is a life-threatening disease. It is characterized by a progressive increase in pulmonary vascular resistance, which leads to pulmonary vascular remodeling. This process involves the abnormal proliferation and resistance to apoptosis of pulmonary artery smooth muscle cells (PASMCs). CHI3L1 has been identified as a novel predictive factor in cardiovascular diseases, where it participates in the morphological and phenotypic transition of smooth muscle cells. We conducted in vivo and in vitro experiments to explore the role and mechanism of CHI3L1 in PAH. Transcriptomic data revealed that CHI3L1 is significantly upregulated in PAH. Single-cell sequencing further demonstrated that CHI3L1 expression was notably increased in PAH macrophages and smooth muscle cells relative to normal controls. In animal experiments, CHI3L1 expression was markedly elevated in the pulmonary arteries of PAH rats, predominantly localized to PASMCs. Inhibiting CHI3L1 expression exogenously alleviated the development of hypoxia+SU5416-induced PAH in rats and reduced pulmonary vascular remodeling. CHI3L1 knockdown suppressed PASMC proliferation and promoted apoptosis under hypoxic conditions in vitro. In contrast, CHI3L1 overexpression led to exacerbated PASMC proliferation and resistance to apoptosis. Furthermore, CHI3L1 promoted PASMC proliferation and PAH progression by modulating the AMPK-AKT signaling pathway, and serum CHI3L1 levels were significantly elevated in PAH rats. Based on preclinical data, this study suggests that targeting CHI3L1 may offer a novel therapeutic strategy for the treatment of PAH. Additionally, serum levels of CHI3L1 could serve as a potential new biomarker for the diagnosis of pulmonary arterial hypertension.
Modulation of miRNA networks by exercise in muscular dystrophies: therapeutic insights and future directions.
Wang Z, Zhao F
Mol Cell Biochem · 2026 Jun · PMID 41894089 · Publisher ↗
Muscular dystrophies (MDs) encompass a diverse group of hereditary disorders characterized by progressive skeletal muscle degeneration and weakness. While current therapeutic strategies primarily focus on symptom managem...
Muscular dystrophies (MDs) encompass a diverse group of hereditary disorders characterized by progressive skeletal muscle degeneration and weakness. While current therapeutic strategies primarily focus on symptom management, physical exercise is increasingly recognized as a potent intervention to attenuate disease progression and preserve muscle function. Recent evidence highlights the critical role of microRNAs (miRNAs)—small non-coding RNAs—in post-transcriptional gene regulation, particularly within muscle biology. Exercise dynamically modulates the expression of specific myomiRs (e.g., miR-1, miR-133, miR-206) and inflammation-associated miRNAs (miR-29, miR-146a), which collectively govern processes such as fibrosis, oxidative stress, and regeneration. This review synthesizes current knowledge on the exercise-mediated regulation of miRNA networks in MDs. We delineate the molecular mechanisms linking physical activity to miRNA biogenesis and examine the downstream therapeutic effects on dystrophic pathology. Furthermore, we critically assess the gap between preclinical success in animal models and the scarcity of human clinical data, proposing a roadmap for developing precision exercise interventions that target miRNA networks to enhance therapeutic outcomes. Precision in this context entails miRNA-guided exercise dosing (e.g., adjusting intensity based on real-time miRNA expression profiles), biomarker-driven personalization (e.g., using circulating miRNAs to tailor regimens for individual patients), and integration with gene or exon-skipping therapies to synergistically address subtype-specific pathologies in MDs such as DMD, BMD, and LGMD.
USP52 impedes malignant progression and cell stemness in prostate cancer by deubiquitinating RBM5 to down-regulate NCAPG2.
Wu H, Wang S, Yang S … +2 more , Sun W, Guan H
Mol Cell Biochem · 2026 May · PMID 41894088 · Publisher ↗
Ubiquitin-specific protease 52 (USP52) is vital to cancer progression by mediating the deubiquitination; however, its biological role and mechanism in prostate cancer (PCa) remain unexplored. Herein, this study aimed to...
Ubiquitin-specific protease 52 (USP52) is vital to cancer progression by mediating the deubiquitination; however, its biological role and mechanism in prostate cancer (PCa) remain unexplored. Herein, this study aimed to discover the functional regulation of USP52 with RNA binding motif protein 5 (RBM5) and non-SMC condensin II complex subunit G2 (NCAPG2) in PCa development and stemness. RT-qPCR and Western blot were applied for expression analysis. Proliferation was assessed by colony formation and EdU assays. Cell metastasis was measured by wound healing migration assay and transwell invasion assay. Cell stemness was detected via sphere formation assay, flow analysis and Western blot detection. USP52 function in tumor growth in vivo was investigated by xenograft tumor assay. Co-immunoprecipitation was conducted for ubiquitination detection. Interaction between RBM5 and NCAPG2 was examined using dual-luciferase reporter assay. PCa samples and cells exhibited the aberrant downregulation of USP52. USP52 overexpression suppressed PCa cell proliferation, migration, invasion and stemness. PCa tumor growth in vivo was hindered by USP52. USP52 stabilized RBM5 protein expression in PCa cells by acting as a deubiquitinating enzyme. RBM5 interacted with NCAPG2 3'UTR and USP52 could down-regulate NCAPG2. USP52 repressed PCa cell progression and stemness via reducing NCAPG2. Thus, USP52 hampered PCa cell development and stemness through removing ubiquitination of RBM5 to control the expression of NCAPG2. USP52 may be used as a therapeutic target for PCa.
A novel cuproptosis-related prognostic gene signature is identified by machine learning and integrative analyses in gliomas.
Ma J, Liu W, Shi X … +4 more , Tang Z, Xiong T, Sun H, Hong Y
Mol Cell Biochem · 2026 May · PMID 41894087 · Full text
Recent studies have highlighted the impact of copper-induced cell death (cuproptosis) on cancer progression, prognosis, and treatment, but it remains unclear whether cuproptosis-related genes (CRGs) play any role in the...
Recent studies have highlighted the impact of copper-induced cell death (cuproptosis) on cancer progression, prognosis, and treatment, but it remains unclear whether cuproptosis-related genes (CRGs) play any role in the glioma tumor microenvironment (TME). The CRGs expression patterns in TCGA glioma samples were evaluated based on genetic and transcriptional alterations identifying three different molecular groupings and showing that CRGs changes were linked to clinical characteristics, prognosis, and TME infiltration. Machine learning algorithms were then used to develop an overall survival score for cuproptosis-related prognostic genes (CRPGs), and its prognostic ability was validated for glioma patients. An elevated CRPGs score indicates a heightened mutation burden, increased glioma metabolism, compromised immunity, and strong correlation with both the cancer stem cells (CSC) index and medication sensitivity to chemotherapeutics. This extensive examination of CRGs in gliomas showed their possible significance in the tumor microenvironment as well as their prognostic value. This extremely precise CRPGs nomogram has furthered our understanding of cuproptosis in gliomas, which will allow new approaches to prognosis and immunotherapy development.
Molecular characteristics of apolipoprotein M and its biological functions in kidney diseases.
Tao J, Tan Y, Yang S … +5 more , Zhang Q, Li Z, Liu Q, Wang H, Cui L
Mol Cell Biochem · 2026 Mar · PMID 41880103 · Publisher ↗
Apolipoprotein M (apoM) is a subclass of apolipoproteins primarily found in high-density lipoprotein (HDL), it was mainly expressed and secreted in the liver and kidneys. ApoM functions as the carrier of sphingosine-1-ph...
Apolipoprotein M (apoM) is a subclass of apolipoproteins primarily found in high-density lipoprotein (HDL), it was mainly expressed and secreted in the liver and kidneys. ApoM functions as the carrier of sphingosine-1-phosphate (S1P) to form apoM-S1P complex, further mediating various physiological and pathological processes in the body. Most research has focused on cardiovascular diseases, such as anti-atherosclerosis, with very few studies in the field of nephrology. In recent years, scholars have found that it plays a crucial role in kidney disease. Thereby, this review would summarize the potential roles of apoM and the apoM-S1P axis in various kidney diseases, including chronic kidney disease, diabetic nephropathy, acute kidney injury, glomerular diseases, and renal clear cell carcinoma, providing new insights for the diagnosis and treatment of kidney diseases.
Ferroptosis in prostatitis: pathogenic mechanisms and therapeutic advances.
Shi J, Zhang Q, Xuan Y … +2 more , Zhang H, Duan Y
Mol Cell Biochem · 2026 Mar · PMID 41863567 · Publisher ↗
Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a complex immune-mediated inflammatory disorder characterized by chronic inflammatory infiltration, oxidative stress, and neuropathic pain in prostate tissue....
Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a complex immune-mediated inflammatory disorder characterized by chronic inflammatory infiltration, oxidative stress, and neuropathic pain in prostate tissue. Elucidating novel pathological mechanisms to develop effective therapeutic strategies remains an urgent research priority. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has recently been implicated in the pathogenesis of various chronic inflammatory conditions. Emerging evidence indicates that ferroptosis activation contributes significantly to CP/CPPS progression, suggesting its targeted regulation as a promising therapeutic approach. However, the precise mechanisms through which ferroptosis regulates chronicity and tissue damage in CP/CPPS require systematic elucidation. This review therefore focuses on elucidating the potential role of ferroptosis in CP/CPPS pathogenesis. We further examine specific pathological evidence linking ferroptosis to prostatitis. Finally, promising compounds that may act as ferroptosis inhibitors in CP/CPPS are summarized.
Cancer-associated fibroblasts-secreted exosomes promote malignant advancement of liver cancer by regulating the circE2F3/miR-1305/E2F3 axis.
Dong W, Liu Y, Yan P … +2 more , Liu F, Cai Y
Mol Cell Biochem · 2026 May · PMID 41849019 · Publisher ↗
Liver cancer is a highly lethal malignancy. Cancer-associated fibroblasts (CAFs) play a key role in regulating tumor progression, in part through the release of exosomes. This study aimed to investigate whether CAF-deriv...
Liver cancer is a highly lethal malignancy. Cancer-associated fibroblasts (CAFs) play a key role in regulating tumor progression, in part through the release of exosomes. This study aimed to investigate whether CAF-derived exosomes contribute to the progression of liver cancer. CAFs were isolated from human liver tumor tissues, and exosomes were subsequently purified from the CAF-conditioned medium. Cell viability was measured using the Cell Counting Kit-8 assay. Cell migration was evaluated by Transwell and wound healing assays. The expression levels of circE2F3, miR-1305, and E2F3 were quantified by quantitative real-time PCR. The interactions among them were validated via luciferase reporter assays and RNA pull-down experiments. CAFs promoted the viability and migration of liver cancer cells. Exosomes derived from CAFs similarly enhanced the proliferative and migratory capacities of these cells. Upon exosomal treatment, circE2F3 expression was upregulated in liver cancer cells. Mechanistically, circE2F3 functioned as a molecular sponge for miR-1305, which directly targets E2F3. Knockdown of circE2F3 suppressed the malignant behaviors of liver cancer cells by modulating the miR-1305/E2F3 axis. Furthermore, inhibiting circE2F3 counteracted the tumor-promoting effects of CAF-derived exosomes, concomitant with altered expression of miR-1305 and E2F3. CAF-derived exosomes promote liver cancer progression by upregulating circE2F3, which in turn sequesters miR-1305 and elevates E2F3 expression. These findings highlight CAF-derived exosomal circE2F3 as a potential therapeutic target for liver cancer.
Loop of N2-polarized neutrophils and exhausted CD8 + T cells induces immunotherapy resistance in NSCLC.
Zou Z, Guo Z, Wei Y … +2 more , Cai S, Yu C
Mol Cell Biochem · 2026 May · PMID 41824204 · Publisher ↗
While neutrophils represent a prominent myeloid component in non-small cell lung cancer (NSCLC), the specific immunosuppressive functions of N2-polarized neutrophils and their mechanistic interactions with CD8⁺ T cells r...
While neutrophils represent a prominent myeloid component in non-small cell lung cancer (NSCLC), the specific immunosuppressive functions of N2-polarized neutrophils and their mechanistic interactions with CD8⁺ T cells remain incompletely characterized. Furthermore, the development of clinically applicable models for prognostic stratification and immunotherapy response prediction, grounded in these molecular interactions, represents a critical unmet need. We integrated large-scale single-cell RNA sequencing datasets to delineate the tumor immune microenvironment, performing pathway enrichment and cell-cell communication analyses. Key molecular features derived from these interactions were employed to construct a deep neural network model. This model was trained and validated on bulk RNA sequencing cohorts to predict immunotherapy response. Additionally, we developed the N2_Neu-CD8⁺ Tex Loop Score (NTLS) for prognostic assessment and evaluated its pan-cancer applicability. Our analysis revealed a previously uncharacterized positive feedback loop between N2 neutrophils and exhausted CD8⁺ T cells (Tex). Neutrophil-derived ICAM1 engages with ITGAL/ITGB2 on CD8⁺ T cells, suppressing their NF-κB signaling and reinforcing the exhausted phenotype. In a feed-forward manner, Tex-derived CCL5 signals via CCR1 on N2 neutrophils, activating their NF-κB pathway and further upregulating ICAM1 expression. This ICAM1-Integrin and CCL5-CCR1 axis creates a self-sustaining immunosuppressive circuit. A deep learning model, built upon genes central to this loop, accurately predicted immunotherapy outcomes in NSCLC and melanoma. The derived NTLS score proved effective for prognostic stratification and was validated across multiple independent cohorts and cancer types. This study defines a pathogenic positive feedback loop, driven by ICAM1-Integrin and CCL5-CCR1 interactions, through which N2 neutrophils and Tex cells cooperatively establish an immunosuppressive niche that drives immunotherapy resistance. The computational models we developed, based on this molecular circuitry, offer robust tools for patient stratification and hold significant translational promise.
RNase A is inhibited by the cysteine-rich protein thionein but not by the metal-containing form metallothionein.
Trujillo-González F, Muñoz-Granados IA, Sanchez-Gaytan BL … +2 more , Brambila E, Perez-Aguilar JM
Mol Cell Biochem · 2026 May · PMID 41824203 · Full text
Metallothionein (MT) is a cysteine-rich protein that displays a high redox activity, acts like an acute phase protein, and forms metal-thiolate clusters. However, little is known about how the presence of metals in MT or...
Metallothionein (MT) is a cysteine-rich protein that displays a high redox activity, acts like an acute phase protein, and forms metal-thiolate clusters. However, little is known about how the presence of metals in MT or their absence in Thionein (T) modify the structure of the protein and if such differential conformations alter the protein-protein interactions that MT/T establishes with other proteins. Ribonucleases (RNases) are a group of enzymes that hydrolyze different classes of RNA and due to the relevance of their function, they are highly regulated by specific inhibitors. Earlier results showed a decrease in RNase activity during an inflammatory process that appears to be a consequence of a de novo synthesis of an unidentified RNase inhibitor (RI) (Brambila et al in Exp Mol Pathol 71:125–131, https://doi.org/10.1006/exmp.2001.2383 , 2001). Therefore, we performed experimental studies to evaluate the ability of MT/T to inhibit RNase A activity in vitro. Computational methods were utilized to characterize the tertiary structure of MT/T in the presence and absence of zinc ions and to evaluate the stability of a complex with RNase A. Our results show that only in the absence of metals, T, the homodimeric protein has an inhibitory effect on RNase A activity via a mechanism that involves the formation of a complex between RNase A and T by specific interactions. Also, the involvement of residues, including cysteines that coordinate the cations, that participate in intermolecular interactions in the metal-bound form, aids in explaining the metal dependent inhibitory properties in the metal-free protein. This work suggests an additional role of T in the regulation of enzyme activity and protein synthesis.
Decoding dexmedetomidine's multiple mechanisms in atherosclerosis: effects on lipid metabolism, inflammation, cholesterol efflux, and foam cell formation.
Zhang M, Yang L, Zhao D
Mol Cell Biochem · 2026 May · PMID 41824202 · Publisher ↗
Atherosclerosis is a leading cause of cardiovascular disease and is characterized by dysregulated lipid metabolism and chronic vascular inflammation. Dexmedetomidine (DEX) has been reported to exert anti-inflammatory, an...
Atherosclerosis is a leading cause of cardiovascular disease and is characterized by dysregulated lipid metabolism and chronic vascular inflammation. Dexmedetomidine (DEX) has been reported to exert anti-inflammatory, antioxidant and lipid-lowering effects across several disease settings, yet its potential therapeutic impact on atherosclerosis remains unclear. In this study, we investigated the anti-atherosclerotic efficacy of DEX and explored the underlying mechanisms in vivo and in vitro. An atherosclerosis model was established by feeding ApoE−/− mice a Western diet for 13 weeks, followed by intraperitoneal injection of DEX (100 µg/kg) for 16 days. Then, RAW264.7 macrophages were exposed to oxidized LDL (Ox-LDL; 50 µg/mL) for 24 h in the presence or absence of DEX (10 µM). Anti-atherosclerotic effects were assessed using Western blotting, quantitative PCR, Oil Red O staining, pathological staining, cholesterol quantification, and serum lipid profiling. DEX treatment markedly reduced lipid-rich plaques in the aortic root and attenuated aortic atherosclerotic lesions in ApoE−/− mice, while also significantly lowering serum glucose (Glu), Ox-LDL, LDL-cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG). In addition, DEX promoted fecal cholesterol excretion, decreased cholesterol accumulation in the liver and intestine, and suppressed systemic expression of TNF-α, IL-6, and IL-1β. Consistently, in Ox-LDL–stimulated RAW264.7 cells, DEX limited foam cell formation and enhanced cholesterol efflux. Mechanistically, both in vivo and in vitro findings indicated that DEX upregulated SIRT1 and ABCA1 expression, whereas pharmacologic inhibition of SIRT1 with selisistat abolished these protective effects, supporting a central role for the SIRT1/ABCA1 axis. Collectively, these results suggest that DEX mitigates atherosclerosis by activating the SIRT1/ABCA1 pathway, thereby alleviating inflammation, foam cell formation, lipid metabolic dysfunction, and impaired cholesterol export, and they highlight DEX as a promising candidate for the treatment and prevention of atherosclerotic disease.
Targeting pH regulation in cancer: combined mild alkaline treatment and NHE1 inhibition as a potential therapy for clear cell renal cell carcinoma.
Celi AB, Mechali A, Beltramone N … +6 more , Casal JJ, Grippo A, Capurro C, Di Giusto G, Ford P, Rivarola V
Mol Cell Biochem · 2026 Apr · PMID 41824201 · Publisher ↗
Acid-base homeostasis is critical for maintaining physiological functions. An acidic tumor microenvironment, driven by altered cellular metabolism, plays a pivotal role in tumor progression by fostering aggressive phenot...
Acid-base homeostasis is critical for maintaining physiological functions. An acidic tumor microenvironment, driven by altered cellular metabolism, plays a pivotal role in tumor progression by fostering aggressive phenotypes, immune evasion, and resistance to therapy, often at the detriment of surrounding normal tissues. The Na⁺/H⁺ exchanger isoform 1 (NHE1) is a key regulator of intracellular pH and a critical factor in cancer cell survival and proliferation. This study aimed to evaluate the effect of mild alkaline treatment, combined with NHE1 inhibition, on cell viability in normal renal cells and clear cell renal cell carcinoma (ccRCC) cells. Our findings reveal that this therapeutic combination selectively induces cell death in ccRCC cells while sparing normal renal cells. Mechanistically, we demonstrate that NHE1 activity is higher in ccRCC cells than in normal cells. In our experimental model, mild alkaline treatment differentially affected NHE1 activity, stimulating it in normal cells but suppressing it in cancer cells. Furthermore, prolonged alkaline exposure alters the subcellular localization of NHE1 in the plasma membrane, with distinct patterns observed between normal and cancer cells. These results suggest that targeting NHE1 activity in conjunction with alkaline treatment represents a promising strategy for ccRCC treatment, providing a potential therapeutic avenue to exploit the differential pH regulation between cancerous and normal cells.
RNF125 promotes CD8 T cell-mediated anticancer immunity and suppresses the malignant phenotype of cervical cancer.
Yang D, Liu J, Gao Y … +2 more , Guan X, Tong R
Mol Cell Biochem · 2026 May · PMID 41824200 · Publisher ↗
Cervical cancer (CC) is a prevalent malignancy in women; however, the efficacy of immunotherapy in this disease is suboptimal, highlighting the need for novel therapeutic targets. We found that low RNF125 expression corr...
Cervical cancer (CC) is a prevalent malignancy in women; however, the efficacy of immunotherapy in this disease is suboptimal, highlighting the need for novel therapeutic targets. We found that low RNF125 expression correlated with poor prognosis in CC patients. In vitro and in vivo, RNF125 inhibited proliferation and induced apoptosis of CC cells. In immunocompetent mice, RNF125 suppressed tumor growth, increased CD8⁺ T cell infiltration, elevated IFN-γ secretion, and reduced PD-1 expression on CD8⁺ T cells. Co-culture experiments confirmed that tumor cells overexpressing RNF125 enhanced CD8⁺ T cell proliferation and function. Further mechanistic investigation revealed that RNF125 promoted CD8⁺ T cell activity by ubiquitinating and degrading PD-L1. Additionally, RNF125 was identified as a direct target of miR-574-5p. This study demonstrates that RNF125 exhibits tumor-suppressive functions in CC by enhancing anti-tumor immunity, highlighting its therapeutic potential.
Unraveling the role of cuproptosis in pulmonary fibrosis pathogenesis and prognosis: an integrative single-cell transcriptomics and microarray analysis.
Chen M, Chen J, Zhang J … +4 more , Zhu Y, Meng X, Yang Z, Wang R
Mol Cell Biochem · 2026 Apr · PMID 41824199 · Publisher ↗
Pulmonary fibrosis (PF), a progressive interstitial lung disease with elusive pathogenesis, remains a therapeutic challenge. Emerging evidence suggests cuproptosis-a copper-dependent cell death pathway-may play a regulat...
Pulmonary fibrosis (PF), a progressive interstitial lung disease with elusive pathogenesis, remains a therapeutic challenge. Emerging evidence suggests cuproptosis-a copper-dependent cell death pathway-may play a regulatory role in disease progression. This study aims to elucidate cuproptosis's biological function and establish a prognostic model for PF. Through integrative analysis of single-cell RNA-seq data from bleomycin (BLM)-induced mouse models and bulk RNA-seq data from idiopathic pulmonary fibrosis (IPF) patients, we identified cuproptosis-related genes (CRGs) using LASSO regression and Cox regression. A novel 4-CRG signature (LIAS, LIPT1, ATP7A, PDHB) was constructed to stratify patients into distinct risk groups in the GSE70866 cohort, where high-risk individuals exhibited poorer survival and enhanced extracellular matrix/lipid metabolism activity via GO/KEGG analysis. Experimental validation in BLM-induced mouse models, TGF-β1-stimulated fibroblast-to-myofibroblast transition assays, and human IPF specimens demonstrated significant downregulation of CRGs through qRT-PCR and immunohistochemical analyses. Functional assays revealed impaired cell viability and elevated cuproptosis markers in fibrotic microenvironments. Our findings establish an inverse correlation between cuproptosis and PF progression, and propose a robust risk-score model for clinical prognosis prediction. This multi-omics approach provides new insights into copper-mediated regulatory mechanisms in fibrogenesis.
Retraction Note: ALKBH5 inhibits thyroid cancer progression by promoting ferroptosis through TIAM1-Nrf2/HO-1 axis.
Li W, Huang G, Wei J … +2 more , Cao H, Jiang G
Mol Cell Biochem · 2026 May · PMID 41811639 · Publisher ↗
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Advances in signaling pathway networks involving LHPP in various diseases.
Cai X, Zhang Y, Zhao L … +3 more , Chang Q, Zhao Y, Liu Z
Mol Cell Biochem · 2026 May · PMID 41733803 · Publisher ↗
Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a newly discovered histidine phosphatase that can remove histidine-linked phosphate groups from proteins, but its function is unclear. Given th...
Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a newly discovered histidine phosphatase that can remove histidine-linked phosphate groups from proteins, but its function is unclear. Given that the LHPP protein might participate in histidine phosphorylation, it is receiving increasing attention from researchers. Recent evidence has suggested that LHPP is a novel tumor suppressor with a crucial role in cancers, as its expression is decreased in different cancers. Previous studies have confirmed that abnormal LHPP levels can lead to overactivation of pathways such as the PI3K/AKT pathway during the course of tumor pathogenesis. In addition, LHPP has been confirmed as a susceptibility gene for depression, which has triggered many related studies. However, the current understanding of the functions of LHPP in diseases is relatively limited, and a systematic summary of its mechanism is lacking. Therefore, this paper reviews relevant studies of LHPP to clarify the mechanism of its involvement in cancers and nervous system diseases and provides new strategies for disease research involving LHPP.
Targeting EIF5A suppresses liver fibrosis through impairment of mitochondrial function in hepatic stellate cells.
Di Y, Jin L, Zhang X … +3 more , Deng P, Gao F, Jin S
Mol Cell Biochem · 2026 Apr · PMID 41729436 · Publisher ↗
Liver fibrosis represents a significant clinical challenge. While targeting activated hepatic stellate cells (HSCs) is a promising therapeutic strategy, the specific role of Eukaryotic Translation Initiation Factor 5 A (...
Liver fibrosis represents a significant clinical challenge. While targeting activated hepatic stellate cells (HSCs) is a promising therapeutic strategy, the specific role of Eukaryotic Translation Initiation Factor 5 A (EIF5A) in this process remains incompletely understood. EIF5A expression was analyzed in human fibrotic liver specimens and experimental mouse models. Its therapeutic potential was evaluated through pharmacological inhibition in fibrotic mice. Direct effects and mechanisms on HSCs were further investigated in vitro, with a focus on mitochondrial function. Immunostaining revealed a marked increase of EIF5A in activated HSCs from human fibrotic livers, which was consistent with findings in mice. Inhibition of EIF5A significantly attenuated liver fibrosis in vivo. Mechanistically, EIF5A deficiency directly impaired mitochondrial function in HSCs, leading to reduced ATP production, decreased mitochondrial membrane potential, and abnormal mitochondrial morphology, thereby suppressing their activation. Our results indicate that EIF5A contributes to HSC activation during liver fibrosis, in part through modulating mitochondrial bioenergetics. The concordant observations in human and mouse systems highlight the translational relevance of EIF5A, supporting its further investigation as a potential therapeutic target for liver fibrosis.
Amelioration of doxorubicin-mediated nephrotoxicity through antioxidant and anti-apoptotic mechanisms of 5,4'-dihydroxy-6,8-dimethoxy-7-O-rhamnosylflavone.
Rajendran P, Alzahrani A, Sekar R … +2 more , Bekhet GM, Balasubramanian R
Mol Cell Biochem · 2026 Apr · PMID 41721972 · Publisher ↗
Doxorubicin (DOX), a cornerstone chemotherapeutic, induces dose-limiting nephrotoxicity through NOX-4-mediated oxidative stress, inflammatory signalling, and apoptosis, thereby compromising its long-term clinical utility...
Doxorubicin (DOX), a cornerstone chemotherapeutic, induces dose-limiting nephrotoxicity through NOX-4-mediated oxidative stress, inflammatory signalling, and apoptosis, thereby compromising its long-term clinical utility. This study investigated whether 5,4'-dihydroxy-6,8-dimethoxy-7-O-rhamnosylflavone (DDR), a bioactive flavonoid, protects against chronic DOX-induced renal injury. To evaluate DDR's renoprotective efficacy and elucidate its mechanistic involvement of NOX-4, NRF2, and apoptotic pathways. Male Swiss albino mice (n = 6/group) received: control vehicle, DOX (2.5 mg/kg i.p., weekly × 6 weeks), DOX + DDR (25 or 50 mg/kg i.p., twice weekly), or DDR alone. Renal function (creatinine, urea, NGAL, KIM-1), oxidative stress markers (MDA, SOD, CAT, GSH), cytokines (pNFκB, TNF-α, IL-6, IL-1β), and protein expression (NOX-4, NRF2, BCL2, BCL-XL, Caspase-3) were quantified. Histopathology employed H&E and Masson's trichrome with semi-quantitative injury scoring. DOX induced severe nephrotoxicity (serum creatinine ↑347%, tubular injury score 14.8 ± 1.4, p < 0.001), characterized by NOX-4 overexpression, NRF2 suppression, and apoptosis (Caspase-3 ↑412%). DDR elicited dose-dependent protection; high-dose DDR restored renal function (creatinine ↓78%), normalized histopathology (score 2.8 ± 0.9, p < 0.001), suppressed NOX and reactivated NRF2, and prevented apoptosis. DDR provides potent, mechanistically defined renoprotection against DOX nephrotoxicity through multi-target modulation of oxidative, inflammatory, and apoptotic pathways. These preclinical findings support DDR's development as a clinically translatable chemotherapeutic adjuvant (Human equivalent dose: 2-4 mg/kg).
Optimization of RNP-CRISPR for high-efficiency gene editing in mouse intestinal organoids.
Cao X, He Y, Guo H … +9 more , Cao X, Zhang D, Lai Y, Yang W, Ma Z, Yu X, Wang L, Li D, Zeng Z
Mol Cell Biochem · 2026 Apr · PMID 41718886 · Full text
Mouse intestinal organoids are ideal models for investigating intestinal development and diseases. The full potential of these models hinges on the ability to precisely engineer their genome, yet traditional methods for...
Mouse intestinal organoids are ideal models for investigating intestinal development and diseases. The full potential of these models hinges on the ability to precisely engineer their genome, yet traditional methods for CRISPR-based editing in 3D cultures often surfer from low efficiency, high cytotoxicity, and inconsistent post-editing differentiation, which limits their applications. Here, we developed an electroporation approach mediated by ribonucleoprotein (RNP)-CRISPR that achieves over 90% gene editing efficiency in mouse intestinal organoids. Using this optimized method, we generated APC-knockout organoids that exhibit Wnt pathway hyperactivation, demonstrated by R-spondin1-independent growth, increased nuclear β-catenin, and enhanced proliferation. Our method addresses a critical technical gap in murine organoid research, offering a scalable platform for intestinal disease modeling.
Current progress in pathway-targeted therapeutics for Alzheimer's disease: mechanistic insights and windows of opportunity.
Ahmad HA, Zafar M, Khan T … +1 more , Khan MI
Mol Cell Biochem · 2026 May · PMID 41712029 · Publisher ↗
Alzheimer’s disease (AD) remains a complex neurodegenerative condition characterized by progressive cognitive decline driven by amyloid-beta (Aβ) plaques, tau neurofibrillary tangles, and neuroinflammation. With extensiv...
Alzheimer’s disease (AD) remains a complex neurodegenerative condition characterized by progressive cognitive decline driven by amyloid-beta (Aβ) plaques, tau neurofibrillary tangles, and neuroinflammation. With extensive research, disease-modifying anti-amyloid monoclonal antibodies have now received U.S. FDA approval for early symptomatic disease; however, benefits remain modest and are accompanied by substantial monitoring and implementation constraints.. This review critically evaluates the current landscape of inhibitor-based therapeutics for AD, encompassing both clinical and preclinical developments, and identifies windows of opportunity for future research. This review synthesizes current progress in inhibitor-based strategies, ranging from cholinesterase inhibitors and NMDA receptor antagonists to amyloid-targeting antibodies, tau-based interventions, and novel anti-inflammatory mechanisms. While agents like Lecanemab show modest cognitive decline reduction, safety and efficacy challenges persist, and small-molecule inhibitors have largely failed. Promising preclinical candidates including multi-target ligands, allosteric modulators, and HDAC6 inhibitors, demonstrate robust effects in animal models, although translation remains elusive. Advances in biomarkers (plasma p-tau217, tau PET) and genetic risk profiling (APOE ε4) are enabling precision approaches, complemented by adaptive designs and AI-driven trial optimization. Integrating multi-target pharmacology with biomarker-guided strategies offers a promising path toward effective, accessible AD therapeutics.
Association between neutrophil percentage-to-albumin ratio and all-cause mortality in patients post-cardiac surgery: a retrospective cohort study.
Lv SB, Lv Q, Luo D
Mol Cell Biochem · 2026 Apr · PMID 41706276 · Publisher ↗
The neutrophil percentage-to-albumin ratio (NPAR) has emerged as a potential prognostic biomarker in the context of cardiac surgery. This study aimed to evaluate the association between NPAR and all-cause mortality (ACM)...
The neutrophil percentage-to-albumin ratio (NPAR) has emerged as a potential prognostic biomarker in the context of cardiac surgery. This study aimed to evaluate the association between NPAR and all-cause mortality (ACM) among patients undergoing cardiac surgery, with the goal of identifying high-risk groups and informing prognostic assessments. Data were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version 3.1) database. Participants were categorized into tertiles based on NPAR values. The primary outcomes were 30-day ACM and 360-day ACM following cardiac surgery. Cox proportional hazards regression and restricted cubic splines (RCS) models were utilized to assess the relationship between NPAR and mortality risk. Kaplan-Meier (K-M) survival analyses were conducted to compare survival probabilities across NPAR tertiles, and subgroup analyses were performed to examine consistency across different strata. A total of 2,101 patients were included in the analysis, of whom 70% were male. The 30-day and 360-day ACM rates were 2% and 6%, respectively. Higher NPAR levels were independently associated with increased risks of both 30-day ACM (adjusted hazard ratio [HR], 2.51; 95% confidence interval [CI] 1.01–6.24) and 360-day ACM (adjusted HR, 2.19; 95% CI 1.29–3.73). The RCS models demonstrated a positive, linear association between NPAR and mortality risk. K-M analyses demonstrated significantly lower survival probabilities in the highest NPAR tertile. Subgroup analyses showed no significant interaction effects. Elevated NPAR values were independently associated with increased risks of 30-day and 360-day ACM following cardiac surgery. These findings suggest that NPAR may be a valuable marker for identifying high-risk patients and improving postoperative risk stratification.
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