Mol. Cell. Biochem. [JOURNAL]
Sun
200 papers
PER1 reduces HIF-1α nuclear accumulation and modulates vascular remodeling in hepatocellular carcinoma.
Zhang Z, Ning C, Mei S … +6 more , Yi C, Tao H, Lu L, Pan S, Wang Z, Tian X
Mol Cell Biochem · 2026 Jul · PMID 42400810 · Publisher ↗
The core clock gene period 1 (PER1) has been reported to possess tumor-suppressive functions; however, its role in regulating tumor vascular abnormalities in hepatocellular carcinoma (HCC) remains incompletely understood...
The core clock gene period 1 (PER1) has been reported to possess tumor-suppressive functions; however, its role in regulating tumor vascular abnormalities in hepatocellular carcinoma (HCC) remains incompletely understood. Here, we integrated bioinformatics analysis with validation using clinical HCC specimens, cell-line experiments, and mouse models to investigate the role of PER1 in vascular structure-related phenotypes, angiogenesis-related factor expression, and hypoxia-inducible factor-1α (HIF-1α) signaling. PER1 was significantly downregulated in HCC tissues, and low PER1 expression was associated with poor patient prognosis. Restoration of PER1 expression inhibited HCC cell growth. Mechanistically, PER1 interacted with HIF-1α at the protein level and reduced its nuclear accumulation without markedly altering HIF-1α mRNA or total protein abundance. This change was accompanied by an angiogenesis-related factor profile characterized by increased TSP-1 and TIMP-2 expression and decreased VEGFA, TGF-β, SDF-1, and FGF-2 expression. Histological analyses further showed that PER1 overexpression was associated with increased CD31-positive vascular structures, enhanced α-SMA-positive perivascular/pericyte-like components, and more continuous collagen IV deposition, whereas PER1 knockdown produced the opposite effects. These findings indicate that PER1 participates in vascular structural remodeling in HCC. Collectively, our study suggests that PER1 modulates HIF-1α-associated angiogenic signaling and vascular structural remodeling, providing new insight into the interaction between circadian rhythm regulation and the HCC vascular microenvironment.
FCGR2A promoter variant reveals shared genetic susceptibility between IBD and stroke.
Wang X, Zhu Z, Li H … +6 more , Gao J, Ding M, Li Y, Shi L, Zhu S, Cheng L
Mol Cell Biochem · 2026 Jul · PMID 42400809 · Publisher ↗
While the epidemiological association between inflammatory bowel disease (IBD) and stroke is well-established, the shared genetic architecture underlying these diseases remains unclear. This study utilized genome-wide as...
While the epidemiological association between inflammatory bowel disease (IBD) and stroke is well-established, the shared genetic architecture underlying these diseases remains unclear. This study utilized genome-wide association studies (GWAS) summary statistics to explore genetic overlaps between IBD and stroke subtypes. Mendelian randomization (MR) was applied to assess potential causal relationships. Cross-trait meta-analysis identified shared loci, followed by colocalization testing to pinpoint causal variants. Furthermore, functional prediction analysis of variants and verification through in vitro experiments. Finally, use mediation MR to explore potential mechanisms in multiple dimensions. We identified eight pairs with potential genetic correlations, with common genetic variants contributing more on ulcerative colitis (UC) and multiple stroke subtypes than Crohn's disease (CD). Among them, there is a potential causal relationship between IBD/UC and large arterial atherosclerotic stroke (LAS), which is consistent with previous epidemiological statistics. In addition, one locus (rs7522794) was initially identified through cross-trait analysis, and colocalization pointed out that the variant rs7522794 on the FCGR2A promoter was the culprit of the comorbid phenotype. The rs7522794-T allele predicted to be more prone to bind SPI1, thereby increasing FCGR2A expression and susceptibility to stroke in IBD patients. Finally, evidence suggests that gut microbes, blood metabolites, and immune cells may play a crucial regulatory role in the shared pathophysiology of IBD/UC and LAS. The study highlights the shared genetics architecture that exists between IBD and stroke, and demonstrates two different (FCGR2A-mediated immune pathways and other indirect regulation) but complementary verification mechanisms, providing new insights into IBD-stroke comorbidities.
Chlamydia psittaci induces GSDME-mediated pyroptosis via the ROS-JNK signaling pathway.
Xiao C, Hu C, Liu Z … +6 more , Wang G, Wang C, Li Z, Bai Q, Chen S, Chen L
Mol Cell Biochem · 2026 Jul · PMID 42400808 · Publisher ↗
Chlamydia psittaci is an obligate intracellular zoonotic pathogen that causes atypical pneumonia. Pyroptosis is a type of regulated cell death mediated by gasdermin-family proteins and plays an important role in the resp...
Chlamydia psittaci is an obligate intracellular zoonotic pathogen that causes atypical pneumonia. Pyroptosis is a type of regulated cell death mediated by gasdermin-family proteins and plays an important role in the response to intracellular infection. This study investigates whether C. psittaci infection triggers GSDME-mediated pyroptosis through the ROS-JNK signaling pathway. Our study revealed that infection with C. psittaci induces pyroptosis through caspase-3 activation and subsequent GSDME cleavage in human cervical epithelial (HeLa) cells. Mechanistically, the infection increased intracellular levels of reactive oxygen species (ROS) and phosphorylated c-Jun N-terminal kinase (JNK). Treatment with either the ROS scavenger NAC or the JNK inhibitor SP600125 significantly suppressed pyroptosis. Furthermore, inhibition of either the caspase-3-GSDME axis or the ROS-JNK pathway significantly increased the number of C. psittaci inclusion bodies. Taken together, our findings suggest that the ROS/JNK signaling pathway modulates GSDME-mediated pyroptosis and concurrently restricts C. psittaci replication in host cells, identifying the ROS-JNK-GSDME axis as a key mechanism in C. psittaci-induced pyroptosis. These findings reveal novel therapeutic targets for the treatment of psittacosis.
Pentraxin 3 is an inflammation-related biomarker that distinguishes early-stage from mid-advanced cardiovascular-kidney-metabolic syndrome.
Xu Z, Yang S, Tan Y … +7 more , Zhang Q, Wang H, Tao J, Liu Q, Li Z, Wang C, Cui L
Mol Cell Biochem · 2026 Jul · PMID 42400807 · Publisher ↗
The cardiovascular-kidney-metabolic (CKM) syndrome represents a continuum linking metabolic dysfunction, chronic kidney disease, and cardiovascular disease, in which chronic inflammation plays a central role. However, co...
The cardiovascular-kidney-metabolic (CKM) syndrome represents a continuum linking metabolic dysfunction, chronic kidney disease, and cardiovascular disease, in which chronic inflammation plays a central role. However, conventional inflammatory biomarkers may not fully capture local inflammatory processes involved in CKM stage transitions. Pentraxin 3 (PTX3), a long pentraxin produced locally at sites of inflammation, may provide complementary information, yet its association with CKM staging has not been systematically evaluated. In this cross-sectional study, circulating PTX3 levels were measured in 240 adults, including healthy controls (stage 0, S0; n = 60) and individuals with stage 2 (S2; n = 60), stage 3 (S3; n = 60), and stage 4 (S4; n = 60) CKM, classified according to the CKM staging framework. Associations between PTX3 and inflammatory, metabolic, cardiac, and renal biomarkers were assessed using Spearman correlation analysis. Multivariable logistic regression models were constructed within the CKM population (S2-S4) to distinguish early-stage CKM (S2) from mid-advanced-stage CKM (S3 + S4). Model discrimination and calibration were evaluated using receiver operating characteristic (ROC) analysis and the Hosmer-Lemeshow goodness-of-fit test. PTX3 levels were significantly elevated in early-stage CKM (S2) compared with healthy controls (p < 0.001) and showed further differentiation between S2 and S3 (p < 0.01). PTX3 showed moderate correlations with biomarkers reflecting inflammatory activation, metabolic dysregulation, myocardial injury, and renal dysfunction, including high-sensitivity C-reactive protein (hs-CRP; r = 0.361, p < 0.001), glycated hemoglobin (HbA1c; r = 0.434, p < 0.001), triglycerides (TG; r = 0.296, p < 0.001), and high-sensitivity cardiac troponin T (hs-cTnT; r = 0.411, p < 0.001), and was inversely correlated with estimated glomerular filtration rate (eGFR; r = -0.419, p < 0.001). In multivariable logistic regression models adjusting for demographic factors, metabolic indices, and cardiorenal biomarkers, PTX3 remained independently associated with classification into mid-advanced-stage CKM (S3 + S4 vs S2; odds ratio [OR] per unit increase = 1.05, 95% confidence interval [CI]: 1.03-1.08; p < 0.001), whereas hs-CRP and procalcitonin (PCT) showed no independent associations. Compared with the clinical base model, addition of PTX3 improved model discrimination, increasing the AUC from 0.833 to 0.892 (ΔAUC = 0.059; DeLong p = 0.008), without evidence of impaired calibration. Circulating PTX3 is cross-sectionally associated with CKM stage classification and demonstrates incremental discriminative value beyond demographic, metabolic, and cardiorenal variables, as well as conventional inflammatory markers, in distinguishing early-stage from mid-advanced-stage CKM. These findings suggest that PTX3 may reflect inflammatory processes not fully captured by systemic markers, supporting its potential role in CKM risk stratification.
High glucose-induced mitochondrial fission promotes Müller cell activation via suppression of the Hippo pathway.
Li B, Wang X, Hao XL … +4 more , Wang Q, Xu B, Peng H, Wang P
Mol Cell Biochem · 2026 Jul · PMID 42397510 · Publisher ↗
Diabetic retinopathy (DR) is the leading cause of blindness in diabetic patients, in which high glucose (HG)-induced Müller cell activation constitutes a central pathological event. This study aimed to untangle the criti...
Diabetic retinopathy (DR) is the leading cause of blindness in diabetic patients, in which high glucose (HG)-induced Müller cell activation constitutes a central pathological event. This study aimed to untangle the critical role and mechanism of mitochondrial fission in this process. We found that under HG conditions, the level of p-Drp1 was significantly elevated (P < 0.05), driving excessive mitochondrial fission. Functional experiments confirmed that artificially enhancing mitochondrial fission directly inhibited the Hippo signaling pathway (levels of core proteins p-MST1/2, p-LATS1, and p-YAP decreased, P < 0.05, and YAP translocated to the nucleus), thereby activating Müller cells (expression of marker proteins GS and Kir4.1 decreased, while expression of GFAP, AQP4, and inflammatory mediators IL-1β, IL-6, VEGF increased, P < 0.05). Key rescue experiments demonstrated that Drp1 silencing (reduced p-Drp1 level, P < 0.05) reversed the aforementioned activation; however, co-administration of the Hippo pathway inhibitor XMU-MP-1 re-induced cell activation, proving that the Hippo pathway is a necessary downstream mediator of mitochondrial fission. In a diabetic rat model, elevated p-Drp1, Hippo pathway inhibition, and cell activation were similarly observed; the mitochondrial fission inhibitor Mdivi-1 alleviated this pathological process, whereas XMU-MP-1 counteracted its protective effects. This study systematically elucidates, from ex vivo to in vivo, the causal regulatory axis of "HG- mitochondrial fission- Hippo pathway inhibition-Müller cell activation," providing experimental evidence and a potential target for developing DR-targeted therapeutic strategies centered on intervening in mitochondrial dynamics.
Correction to: Estradiol inhibits vascular endothelial cells pro-inflammatory activation induced by C-reactive protein.
Cossette É, Cloutier I, Tardif K … +2 more , DonPierre G, Tanguay JF
Mol Cell Biochem · 2026 Jul · PMID 42384347 · Publisher ↗
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Galectin-3, transforming growth factor beta 1, and brain natriuretic peptide in cardiac remodeling under hyperlipidemic and hyperglycemic stress.
Patel H, Pathak A, Rajalekshmi R … +2 more , David B, Agrawal DK
Mol Cell Biochem · 2026 Jul · PMID 42384346 · Publisher ↗
Hyperlipidemia (HYL) and hyperglycemia (HYG) directly drive pathological cardiac remodeling; however, the mechanisms by which these conditions differentially regulate profibrotic signaling and early stress‑response pathw...
Hyperlipidemia (HYL) and hyperglycemia (HYG) directly drive pathological cardiac remodeling; however, the mechanisms by which these conditions differentially regulate profibrotic signaling and early stress‑response pathways in left ventricular (LV) myocardium remain poorly defined. This study investigated the expression and localization of galectin-3 (Gal-3), transforming growth factor-β1 (TGF-β1), and brain natriuretic peptide (BNP) in a Yucatan miniswine model of HYL and HYG. Female Yucatan miniswine were assigned to normal control, HYL (high-cholesterol diet), or HYG (high-fat/high-carbohydrate diet plus low dose streptozotocin) groups (n = 6/group) for 8-weeks, and LV tissue was assessed by histology, qRT-PCR, Western blot, and immunohistochemistry. Both metabolic conditions induced cardiomyocyte hypertrophy and interstitial fibrosis, with more diffuse collagen deposition in HYG myocardium. qRT-PCR demonstrated upregulation of Gal-3, TGF-β1, and BNP relative to controls, with transcript levels positively correlating with circulating glucose concentration. Western blot analysis showed relatively greater active TGF-β1 signal in HYL myocardium and greater latent precursor accumulation in HYG myocardium, suggesting condition-associated differences in TGF-β1 regulation. Immunohistochemistry demonstrated perivascular Gal-3 localization, cytoplasmic and perinuclear TGF-β1 immunoreactivity in cardiomyocytes, and BNP immunoreactivity predominantly within subendocardial Purkinje fibers, with increased staining intensity in metabolically stressed groups compared with controls. Collectively, these findings suggest that HYL and HYG are associated with overlapping but distinct patterns of Gal-3, TGF-β1, and BNP expression during metabolic cardiac remodeling. The Gal-3/TGF-β1 axis may represent a shared profibrotic pathway, whereas BNP may reflect a compensatory stress response whose functional significance requires further mechanistic validation.
Ellagic acid from the traditional Chinese medicinal herb Scutellaria barbata may accelerates apoptosis in hepatic stellate cells during liver fibrosis via inhibiting miR-182-5p.
Li F, Liu Z, Wang B … +3 more , Liang J, Liu J, Wei X
Mol Cell Biochem · 2026 Jul · PMID 42384345 · Publisher ↗
Liver fibrosis is usually accompanied by abnormal activation of hepatic stellate cells. Exosomal microRNAs play important roles in the development of liver fibrosis. Our previous study confirmed that Ellagic acid (EA) is...
Liver fibrosis is usually accompanied by abnormal activation of hepatic stellate cells. Exosomal microRNAs play important roles in the development of liver fibrosis. Our previous study confirmed that Ellagic acid (EA) is one of the main bloodstream components of Scutellaria barbata, a traditional Chinese medicinal herb. This study aimed to explore the effects of EA on hepatic stellate cells in liver fibrosis. First, a CCl-induced mouse model of liver fibrosis was used to evaluate the effects of EA administration on the histopathology and histochemical staining of liver tissue in mice with liver fibrosis, while simultaneously assessing serum markers of liver function; Second, RT-PCR was used to detect fibrosis-related genes, inflammation-related genes and matrix metalloproteinase-related genes. Third, exosome-enriched fraction miRNAs from liver tissues were sequenced and PCR-verified for differential expression. Finally, in vitro experiments were performed on murine hepatic stellate cells (JS-1) and human hepatic stellate cells (LX-2) using flow cytometry and Western blotting (WB) to apoptosis-related proteins. Animal studies demonstrated that Scutellaria barbata and its natural active component EA can significantly ameliorate hepatic histopathology in the mouse model of liver fibrosis. Furthermore, EA effectively improves serum liver function parameters, reduces the expression of fibrosis-related, inflammation-related and matrix metalloproteinase-related genes, and markedly reduces elevated miR-182-5p expression in the fibrotic model. Cellular experiments demonstrated that inhibition of miR-182-5p promotes the expression of proteins associated with apoptosis in hepatic stellate cells, thereby accelerating apoptosis in these cells. In summary, EA from S. barbata may accelerates hepatic stellate cell apoptosis during liver fibrosis by inhibiting miR-182-5p.
GeneQuantify: a web-based tool for qPCR gene expression and copy number variation analysis.
Yalçınkaya B
Mol Cell Biochem · 2026 Jul · PMID 42384344 · Publisher ↗
Quantitative polymerase chain reaction (qPCR) is an indispensable tool in clinical biochemistry laboratories for gene expression and copy number variation (CNV) analyses. However, the interpretation of qPCR data includin...
Quantitative polymerase chain reaction (qPCR) is an indispensable tool in clinical biochemistry laboratories for gene expression and copy number variation (CNV) analyses. However, the interpretation of qPCR data including normalization, rigorous statistical testing, and professional visualization typically requires advanced bioinformatics expertise. This study aimed to develop a user-friendly, web-based platform that integrates robust statistical frameworks and quality control modules for streamlined and standardized qPCR data evaluation. GeneQuantify is freely accessible at https://GeneQuantify.streamlit.app/ and its source code is openly available at https://github.com/burhanettiny/GeneQuantify (GPL-3.0 license). GeneQuantify, a web-based application developed using Python and Streamlit, allows for the input of target and reference gene Cq values via manual entry or direct import from spreadsheet software or standardized RDML/RDES file formats. The platform automatically calculates ΔCq, ΔΔCq, and relative expression levels using the 2 method. Integrated features include multi-reference gene normalization (geNorm), automated outlier detection (Grubbs' test or Interquartile Range), and amplification efficiency correction (Pfaffl model). ΔCt values are subjected to normality (Shapiro-Wilk) and variance homogeneity (Levene's) testing to ensure statistical validity. The platform features an automated statistical decision pipeline (Shapiro-Wilk → Levene → t/Welch/Mann-Whitney/ANOVA/Kruskal-Wallis) with Bonferroni and Benjamini-Hochberg FDR corrections. A six-language interface (Turkish, English, German, French, Spanish, and Arabic) ensures international accessibility. Platform accuracy was validated against manual Excel-based calculations across seven predefined test scenarios, yielding consistent results in all cases. GeneQuantify provides a highly accessible, integrated qPCR analysis environment that consolidates automated calculations, quality control, statistical decision-making, and visualization. By aligning with MIQE guidelines and offering RQ-based automated statistical selection, the platform enhances reproducibility, transparency, and workflow efficiency in molecular research, clinical biochemistry, and educational settings.
NCAPG reprograms glycolytic and lipid metabolism by sustaining glycerophospholipid flux in small-cell lung cancer.
Sun Y, Wen J, Su R … +1 more , Liu L
Mol Cell Biochem · 2026 Jul · PMID 42384343 · Publisher ↗
Small-cell lung cancer (SCLC) is characterized by rapid growth and a pronounced neuroendocrine phenotype, accompanied by marked metabolic plasticity. Although metabolic reprogramming is a hallmark of SCLC, the molecular...
Small-cell lung cancer (SCLC) is characterized by rapid growth and a pronounced neuroendocrine phenotype, accompanied by marked metabolic plasticity. Although metabolic reprogramming is a hallmark of SCLC, the molecular mechanisms coordinating glycolytic and lipid metabolic pathways remain poorly defined. Untargeted metabolomic profiling and RNA sequencing were performed on 46 surgically resected SCLC tissues, 39 paired non-tumorous lung tissues, and corresponding serum samples to identify dysregulated metabolic pathways and key regulatory genes. NCAPG expression and function were evaluated using quantitative real-time PCR, Western blotting, Seahorse extracellular flux analysis, and xenograft mouse models. Cell proliferation, apoptosis, ATP production, and reactive oxygen species (ROS) levels were quantified using standard biochemical and flow cytometric assays. Metabolomic analysis identified 438 significantly altered metabolites in SCLC, including 215 shared between tumor tissues and serum samples, indicating systemic metabolic reprogramming. Pathway enrichment analysis revealed marked activation of glycolysis, glycerophospholipid metabolism, and oxidative phosphorylation. Transcriptomic profiling identified NCAPG as one of the most upregulated genes in SCLC (fold change = 4.7, FDR < 0.001), with elevated expression associated with advanced pathological stage and poor overall survival (HR = 1.47, P = 0.002). Functional depletion of NCAPG in H69 and H446 cells reduced cell viability by 45-60% and increased apoptosis approximately twofold. Seahorse analysis demonstrated a ~ 40% reduction in extracellular acidification rate accompanied by increased oxygen consumption, indicating a metabolic shift from glycolysis toward oxidative phosphorylation. In vivo, NCAPG knockdown suppressed xenograft tumor growth by 58% and significantly downregulated key glycolytic and glycerophospholipid enzymes, including HK2, LDHA, and CHPT1. NCAPG promotes metabolic reprogramming in SCLC by sustaining coupled glycolytic and glycerophospholipid flux, thereby supporting tumor energy production and biosynthetic demands. Targeting this NCAPG-mediated metabolic axis may represent a promising therapeutic strategy for small-cell lung cancer.
Combination of sitagliptin and mangiferin mitigates testicular damage induced by paclitaxel via mediating Sestrin2/Keap1/Nrf2 signaling pathway.
El-Beheiry KM, El-Shitany NA, El-Sayad ME … +1 more , Elsisi AE
Mol Cell Biochem · 2026 Jul · PMID 42384342 · Publisher ↗
Oncofertility is an emergent discipline that combines many strategies to preserve fertility for cancer patients who are at risk of becoming infertile due to the gonadotoxicity of therapy. Although paclitaxel (PTX) is fre...
Oncofertility is an emergent discipline that combines many strategies to preserve fertility for cancer patients who are at risk of becoming infertile due to the gonadotoxicity of therapy. Although paclitaxel (PTX) is frequently used as an antineoplastic, testicular damage is regretfully linked to its use. Sitagliptin (SIT) and mangiferin (MAN) have promising antioxidant, anti-inflammatory, and anti-apoptotic actions. Thus, the goal of this study is to explore the ameliorative impact of SIT, MAN, and their combination on the PTX-provoked testicular toxicity model. Testicular toxicity is triggered by a single dose of PTX (8 mg/kg). Adult male albino rats were randomly classified into 5 equal groups: control, PTX, and PTX groups treated with SIT, MAN, or their combination for 14 days. The testes and epididymides were gathered for biochemical assessments and sperm analysis, respectively. Histopathological, ultrastructural, and immunohistochemical examinations of caspase-3, cleaved caspase-3, NLRP3, Nrf2, and Keap1 were investigated. Treated groups with SIT, MAN, or their combination significantly increased serum testosterone, testicular LDH-C content, sperm count, and motility compared to PTX group. Testicular catalase activity, Nrf2, and sestrin2 levels were significantly elevated compared to the PTX group. The treated groups counteracted the increase in serum ALP, ACP, LDH-C, testicular MDA, caspase-1, IL-1ꞵ, and IL-18 contents, NLRP3, Keap1, caspase-3, and cleaved caspase-3 expressions induced by PTX. Such therapeutic effects were more pronounced in combination than monotherapy. In conclusion, our study found that combining SIT and MAN had a remarkably beneficial impact on PTX-induced testicular toxicity by mediating the Sestrin2/Keap1/Nrf2 signaling pathway.
Next-generation sequencing reveals aqueous MicroRNA and piRNA signatures in age-related macular degeneration and polypoidal choroidal vasculopathy.
Wang L, Guo ZY, Hu FX … +6 more , Zhang CY, Yuan Y, Zhou BQ, Peng YT, Pang L, Wang Y
Mol Cell Biochem · 2026 Jul · PMID 42384341 · Publisher ↗
MicroRNAs (miRNAs) play important roles in the pathogenesis of age-related macular degeneration (AMD), while whether polypoidal choroidal vasculopathy (PCV) represents a subtype of AMD remains controversial. However, the...
MicroRNAs (miRNAs) play important roles in the pathogenesis of age-related macular degeneration (AMD), while whether polypoidal choroidal vasculopathy (PCV) represents a subtype of AMD remains controversial. However, the differential small non-coding RNA profiles in aqueous humor (AH) between neovascular AMD (nAMD) and PCV remain insufficiently characterized. Therefore, this study aimed to characterize miRNA and piRNA expression profiles in AH samples from nAMD and PCV patients and to explore the potential involvement of these small non-coding RNAs in angiogenesis-related pathways. AH samples were collected from nine cataract controls, eight treatment-naïve nAMD patients, and eight treatment-naïve PCV patients. Small RNA profiles in AH were analyzed using next-generation sequencing (NGS). Differential expression analysis was performed using DESeq2 with adjustment for age, sex, best-corrected visual acuity (BCVA), intraocular pressure (IOP), batch effects, and quality-control covariates. Target gene prediction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently conducted. Selected miRNAs were partially validated by quantitative PCR (qPCR). To further evaluate their potential relevance to angiogenesis, expression levels of selected miRNAs were additionally examined in a laser-induced choroidal neovascularization (CNV) mouse model. A total of 35 differentially expressed miRNAs were identified between nAMD and PCV, including 28 upregulated and 7 downregulated miRNAs. Moreover, 27 and 47 uniquely expressed miRNAs were detected in nAMD and PCV, respectively. Four miRNAs exhibited opposite expression patterns between the two diseases. Functional enrichment analysis revealed significant involvement of Hippo, MAPK, and neurodegeneration-related signaling pathways. qPCR validation confirmed the differential expression of miR-150-5p and VEGF. In the laser-induced CNV mouse model, miR-150-5p showed expression changes consistent with the human AH sequencing results. Distinct miRNA and piRNA expression profiles were identified between nAMD and PCV, suggesting differential molecular mechanisms underlying the two diseases. These findings improve our understanding of AMD and PCV pathogenesis and may provide potential biomarkers for disease differentiation and angiogenesis-related research.
Clinical plausibility of eggshell membrane proteins for osteoarthritis: a study of solubility, digestibility, and immune response.
Gegel S, Kumar A, Goudeva L … +1 more , Borlak J
Mol Cell Biochem · 2026 Jul · PMID 42384340 · Publisher ↗
Supplements are commonly used by osteoarthritis (OA) patients, and eggshell membrane (ESM) proteins are widely advertised as natural bioactive compounds for joint health. Here, we evaluated the solubility, digestibility,...
Supplements are commonly used by osteoarthritis (OA) patients, and eggshell membrane (ESM) proteins are widely advertised as natural bioactive compounds for joint health. Here, we evaluated the solubility, digestibility, and immunomodulatory potential of commercial ESM supplements under physiologically relevant conditions to assess their plausibility as anti-inflammatory agents. We analyzed three commercial ESM formulations (NEM, Torolis, and Biova) using standardized extraction protocols. Protein solubility was assessed in physiological saline and under simulated gastric (pH 2) and intestinal (pH 5.8) conditions with controlled temperature, agitation, and digestive enzyme exposure. We examined the role of disulfide-crosslinked proteins in insolubility using dithiothreitol (DTT) and evaluated digestibility of proteins by SDS-PAGE after treatment with pepsin, pancrelipase (Creon), or sequential digestion. Released peptides were identified by MALDI-TOF mass spectrometry, and immunomodulatory effects were tested using human peripheral blood mononuclear cells (PBMC) by measuring cytokine release after stimulation with lipopolysaccharide or Phorbol 12-myristate 13-acetate/Ionomycin, in the presence or absence of Biova. NEM and Torolis showed extremely low solubility (< 0.3%) and remained insoluble under all conditions, including after DTT treatment. Although Biova was highly soluble (~ 90%), simulated gastrointestinal digestion produced minimal peptide generation. Only non-physiological extraction yielded sporadic trace peptides, most lacking known anti-inflammatory relevance. In PBMC assays, Biova increased IL-6 after lipopolysaccharide stimulation, showed a non-significant TNFα reduction, and had no effect on IL-17 A or granzyme B. Together, commercial ESM supplements are largely insoluble, resistant to digestion, and show no meaningful anti-inflammatory activity in human immune cells. These findings challenge the plausibility of orally administered ESM as a therapeutic intervention for osteoarthritis.
Bile acid-induced TBG depletion promotes trophoblast apoptosis via local thyroxine insufficiency in intrahepatic cholestasis of pregnancy.
Wang G, Hu W, Gao J … +3 more , Wang R, Zhang T, Dong R
Mol Cell Biochem · 2026 Jun · PMID 42371391 · Publisher ↗
Intrahepatic cholestasis of pregnancy (ICP) is characterized by bile acid accumulation, placental dysfunction, and adverse perinatal outcomes. However, there is currently no reliable tool to predict the occurrence of sev...
Intrahepatic cholestasis of pregnancy (ICP) is characterized by bile acid accumulation, placental dysfunction, and adverse perinatal outcomes. However, there is currently no reliable tool to predict the occurrence of severe ICP or its associated complications, and its pathophysiology remains incompletely understood. The objective of this study was to identify more sensitive and specific biomarkers for the clinical diagnosis, early prediction, and prognostic assessment of adverse outcomes in ICP, and to explore the biological relevance of the identified pathway at the maternal-fetal interface. We performed integrated serum metabolomic-proteomic analysis, followed by trimester-specific clinical validation, placental tissue analysis, in vitro trophoblast experiments, and in vivo validation in an estrogen-induced ICP rat model. Exploratory multi-omics analysis highlighted the thyroxine-binding globulin-thyroxine (TBG-T4) axis, related to thyroid hormone transport and availability, as a biologically relevant pathway in ICP. Although total and free T4 remained within physiological reference ranges, circulating TBG, total T4, and free T4 were significantly reduced across pregnancy in women with ICP and were associated with biochemical cholestasis, earlier delivery, and lower neonatal birth weight. Mechanistic analyses showed that reduced TBG availability was associated with decreased local T4 availability and enhanced trophoblast apoptosis under bile acid stress. In the ICP rat model, Ad-TBG-mediated TBG overexpression partially restored thyroid hormone homeostasis, attenuated placental and hepatic injury, and improved fetal growth and survival. These findings identify disruption of the TBG-T4 axis as a mechanistic link between cholestatic stress, impaired thyroid hormone availability, and trophoblast apoptosis in ICP.
The factors between BMI and diabetic nephropathy and protective role of the FGF21-SIRT1 axis in diabetic nephropathy.
Liu C, Zhang Q, Zhang Y
Mol Cell Biochem · 2026 Jun · PMID 42348140 · Publisher ↗
Obesity and diabetic nephropathy (DN) represent escalating global health burdens. Glomerular mesangial cell (MC) injury, driven by lipotoxicity from free fatty acids like palmitic acid (PA), is central to DN pathogenesis...
Obesity and diabetic nephropathy (DN) represent escalating global health burdens. Glomerular mesangial cell (MC) injury, driven by lipotoxicity from free fatty acids like palmitic acid (PA), is central to DN pathogenesis. Fibroblast growth factor 21 (FGF21) regulates metabolism and mitigates obesity-related complications, yet its specific protective mechanisms against PA-induced MC injury remain unclear. This study employed a dual approach. Part I involved a cross-sectional survey of 1,067 type 2 diabetes mellitus (T2DM) patients to identify demographic and clinical risk factors for chronic kidney disease (CKD) using multivariate regression and latent class analysis. Part II utilized human MCs to investigate PA-induced apoptosis and endoplasmic reticulum stress (ERS), evaluating the therapeutic potential of recombinant human FGF21 (rhFGF21) and the involvement of the SIRT1 signaling pathway. A total of 1067 patients with T2DM were involved in the current study, among them, 345 patients with chronic kidney disease (CKD). The percent of females was 50.3%, and the mean age was 59 ± 11.3 years. Multivariate regression analysis showed that age, systolic blood pressure (SBP), duration of diabetes, hyperlipidemia and smoking status were associated with DN. We also performed a potential category analysis of these factors, and the results were derived into three groups. Further analysis found that there was a positive association between the stage of diabetes and the risk factors at high risk levels. We identified that PA increased the levels of pro-apoptotic markers (cleaved caspase-3 and BCL-2 associated X-protein), decreased the expression levels of the anti-apoptotic marker BCL-2, and upregulated the expression levels of the endoplasmic reticulum stress (ERS)-related proteins, glucose-regulated protein 78, activation transcription factor 4, and CHOP. However, all the effects were attenuated by rhFGF21 treatment. In addition, PA increased FGF21 and sirtuin 1 (SIRT1) expression levels, and rhFGF21 further upregulated SIRT1 expression. However, upon SIRT1 knockdown, rhFGF21 did not exert its protective effect on human MCs. Our findings demonstrate that rhFGF21 protects human MCs from PA-induced apoptosis and ERS via the FGF21-SIRT1 signaling cascade. Integrating these molecular insights with clinical risk stratification suggests that targeting the FGF21-SIRT1 pathway, alongside managing modifiable risk factors such as hypertension and hyperlipidemia, offers a promising integrated strategy for preventing and treating diabetic nephropathy.
Naringenin inhibits endothelial-mesenchymal transition and alleviates myocardial fibrosis in rats by regulating the AKT/GSK3β/β-catenin pathway.
Huang K, Shao C, Zhou H … +4 more , Xu G, Li B, Jin C, Wan H
Mol Cell Biochem · 2026 Jun · PMID 42348139 · Publisher ↗
Endothelial-mesenchymal transition (EndMT) is increasingly recognized as a critical factor contributing to myocardial fibrosis, which ultimately leads to cardiac dysfunction. Naringenin (NAR), a major flavonoid derived f...
Endothelial-mesenchymal transition (EndMT) is increasingly recognized as a critical factor contributing to myocardial fibrosis, which ultimately leads to cardiac dysfunction. Naringenin (NAR), a major flavonoid derived from citrus fruits, exhibits various pharmacological properties, including anti-inflammatory, antioxidant, and cardioprotective effects. However, the pharmacological mechanism by which NAR counteracts EndMT remains unclear. In this study, a heart failure model was established in rats by subcutaneous injection of isoproterenol hydrochloride (ISO, 5 mg/kg for 7 days), and human umbilical vein endothelial cells (HUVECs) were stimulated with angiotensin II (Ang II, 1 µM) in vitro. NAR was administered orally (50 and 100 mg/kg/day) for 28 days after ISO induction. Echocardiography revealed that NAR significantly improved ejection fraction (EF) and fractional shortening (FS), and reduced systolic/diastolic diameters and volumes. Histological analyses (H&E and Masson's trichrome staining) showed that NAR attenuated ISO‑induced myocardial disarray, hypertrophy, and collagen deposition. Immunohistochemistry and Western blot demonstrated that NAR downregulated fibrosis markers (collagen I, collagen III) and the mesenchymal marker α‑SMA, while upregulating the endothelial marker CD31. Mechanistically, NAR increased the phosphorylation of AKT and GSK3β, as well as the expression of β‑catenin, indicating activation of the AKT/GSK3β/β‑catenin pathway. Consistently, the GSK3β inhibitor AR‑A014418 reversed the protective effects of NAR in HUVECs. In summary, our findings demonstrate that naringenin attenuates myocardial fibrosis by inhibiting EndMT via modulation of the AKT/GSK3β/β‑catenin signaling pathway. These results highlight the promising therapeutic potential of naringenin in managing myocardial fibrosis.
P2Y12-AMPKα2 signaling contributes to cardiomyocyte senescence in doxorubicin-induced heart failure.
Niu Q, Wang H, Zhao M … +8 more , Zhang H, Hao R, Liu P, Guo L, Chen B, Xi Y, Li P, Yin Y
Mol Cell Biochem · 2026 Jun · PMID 42340549 · Publisher ↗
Doxorubicin (DOX)-induced cardiotoxicity is closely associated with oxidative stress, DNA damage, and senescence-related cardiac injury. This study evaluated the protective effects of Floralozone against DOX-induced card...
Doxorubicin (DOX)-induced cardiotoxicity is closely associated with oxidative stress, DNA damage, and senescence-related cardiac injury. This study evaluated the protective effects of Floralozone against DOX-induced cardiac injury and explored the associated molecular changes. Floralozone alleviated DOX-induced cardiac dysfunction, myocardial structural damage, oxidative stress, DNA damage responses, and senescence-related changes in vivo and in vitro. These protective effects were accompanied by modulation of the P2Y12-AMPKα2-ASK1-MEK3-related stress signaling axis. These findings suggest that Floralozone may protect against DOX-induced cardiac injury by suppressing oxidative stress, attenuating DNA damage responses, and reducing senescence-related signaling.
Synthesis and multilevel evaluation of benzimidazole-based anticancer compounds: DNA/serum albumin interaction, and in-depth theoretical insights.
Kundu S, Akkoc S, Erzurumlu Y … +3 more , Alhag SK, Alkeridis LA, Feizi-Dehnayebi M
Mol Cell Biochem · 2026 Jun · PMID 42334525 · Publisher ↗
Within the scope of this investigation, two novel compounds (3a and 3b) were designed and synthesized in two steps. Compounds 3a and 3b were tested utilizing the MTT study to evaluate their in vitro cytotoxic activity ag...
Within the scope of this investigation, two novel compounds (3a and 3b) were designed and synthesized in two steps. Compounds 3a and 3b were tested utilizing the MTT study to evaluate their in vitro cytotoxic activity against healthy human embryonic kidney, lung cancer, breast cancer, and human liver cancer cell lines. It was determined that compound 3b exhibited high levels of cytotoxic activity against both liver and breast cancer cell lines, with IC values of 10.83 and 11.55 µM, respectively. Also, to elucidate the anticancer mechanism of compounds, pro-apoptotic BAX and BiD, anti-apoptotic BCL2 and BCL-xl, oxidant enzymes PRDX1 and SOD1 levels were examined by RT-qPCR. Moreover, cellular oxidative stress levels were spectrophotometrically measured, and cellular senescence was evaluated via the senescence-associated β-galactosidase test. DFT calculations and RDG, ELF, and LOL analyses were performed to demonstrate the reactivity of these compounds. Compounds significantly down-regulated anti-apoptotic genes, whereas mRNA levels of pro-apoptotic genes were up-regulated in MCF-7 cells. Moreover, oxidative stress status was significantly increased depending on the compound treatment. Consistently, PRDX1 and SOD1 levels were also significantly up-regulated. Furthermore, cellular senescence was significantly induced by the compounds. Fluorescence spectroscopy demonstrated strong binding of both compounds with CT-DNA, characterized by static quenching mechanism and binding constants of 6.02 × 10M(for 3a) and 8.69 × 10M(for 3b), suggesting an intercalative binding mode. In contrast, moderate affinity toward BSA indicated suitable transport characteristics with reduced nonspecific protein binding. Molecular docking studies supported the experimental findings. These combined results verify the potential of the synthesized derivatives as promising candidates for further investigation as biologically active anticancer agents.
Hijacking the cytoskeleton: association of HCV polymerase with α/β-tubulin and its potential relation to the viral replication and cell proliferation.
Ali AA
Mol Cell Biochem · 2026 Jun · PMID 42334524 · Publisher ↗
Hepatitis C virus (HCV) manipulates host cellular pathways to create favourable conditions that support its replication and persistence. Identifying virus-host interactions helps to prevent disease progression and suppor...
Hepatitis C virus (HCV) manipulates host cellular pathways to create favourable conditions that support its replication and persistence. Identifying virus-host interactions helps to prevent disease progression and supports the development of host-directed antiviral therapies (HDTs) with a reduced risk of drug resistance due to viral mutations. In this study, a proteomic approach using in vitro pulldown assay and mass spectrometry identified α- and β-tubulin as novel cellular proteins physically associated with the viral RNA-dependent RNA polymerase (NS5B). This association was validated in hepatic (Huh7) and non-hepatic (HEK293T) cells. Further analysis confirmed that the interaction between NS5B and α/β-tubulin is an indirect interaction mediated by unidentified protein(s). Domain mapping analysis using NS5B-deletion mutants localized the tubulin-interacting region of NS5B to its N-terminal domain. Nocodazole, a known inhibitor of α- and β-tubulin polymerization, significantly reduced the association between NS5B and α-tubulin in vitro and in vivo settings, but had no notable impact on the NS5B/β-tubulin interaction. Additionally, nocodazole treatment markedly inhibited RNA replication of HCV subgenomic replicon in Huh7 cells in a dose-dependent manner. These results suggest an association between tubulin proteins and HCV RNA replication, potentially involving the interaction with NS5B. In addition, NS5B expression was associated with increased cell proliferation, indicating a possible link between NS5B/tubulin interaction, microtubule dynamics, and cellular transformation. Further studies are required to determine whether these associations reflect direct functional roles in HCV RNA replication, trafficking, virus assembly and/or cellular transformation.
RBM15 promotes hyperglycemia-induced retinal endothelial cell injury by regulating FOXO3 stability via m6A modification.
Yu Y, Ren Y, Dong S … +2 more , Yao J, Chen Z
Mol Cell Biochem · 2026 Jun · PMID 42334523 · Publisher ↗
Diabetic retinopathy (DR), a common microvascular complication of diabetes mellitus, is a leading cause of vision loss among working-age adults. Although N6-methyladenosine (m6A), a prevalent post-transcriptional mRNA mo...
Diabetic retinopathy (DR), a common microvascular complication of diabetes mellitus, is a leading cause of vision loss among working-age adults. Although N6-methyladenosine (m6A), a prevalent post-transcriptional mRNA modification, is emerging as a key regulator in DR, the specific role of the m6A writer RBM15 in hyperglycemia-induced retinal endothelial cell injury remains poorly defined. Here, we found that RBM15 is upregulated in the retinas of diabetic mice as well as in endothelial cells (ECs) challenged with high glucose (HG). Knockdown of RBM15 significantly mitigated HG-induced apoptosis and rescued autophagy deficiency in retinal ECs. In vivo, downregulation of RBM15 effectively attenuated retinal thinning, acellular capillary formation, and vascular leakage in diabetic mice. Mechanistically, we demonstrated that RBM15 regulates HG-induced apoptosis and autophagy deficiency in ECs by modulating FOXO3 mRNA stability in an m6A-dependent manner. In conclusion, our findings identify the RBM15/m6A/FOXO3 signaling pathway as a critical regulator of HG-induced retinal microvascular dysfunction and highlight RBM15 as a potential therapeutic target for the treatment of DR.
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