Biochemical Genetics[JOURNAL]
Sun
200 papers
VALD-3 Induces GSDME-Dependent Pyroptosis via ROS/JNK/Bax Pathway in Triple-Negative Breast Cancer Cells.
Zhao X, Pan X, Ma W … +6 more , Liang S, Da D, Liu J, Zhang L, Song P, Li H
Biochem Genet · 2026 Jul · PMID 42384357 · Publisher ↗
Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer, known for its high malignancy, elevated risk of recurrence and metastasis, and limited therapeutic options, resulting in the poo...
Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer, known for its high malignancy, elevated risk of recurrence and metastasis, and limited therapeutic options, resulting in the poorest prognosis among breast cancer types. This study explores the anticancer effects of VALD-3, a Schiff base ligand derivative, on breast cancer cells. While VALD-3 exhibited cytotoxic effects on both triple-negative breast cancer (TNBC) and estrogen receptor-positive (ER+) MCF-7 cells, it more potently inhibited TNBC cell viability. More importantly, VALD-3 induced characteristic pyroptotic features selectively in TNBC cells, including cell swelling, balloon-like protrusions, and the release of inflammatory cytokines due to pore formation in the plasma membrane, ultimately inhibiting tumor growth. Mechanistically, VALD-3 increased reactive oxygen species (ROS) levels and JNK phosphorylation, leading to the recruitment of Bax to the mitochondria and the formation of a Bax-Bcl-2 heterodimer, which facilitated cytochrome c release into the cytoplasm. This cascade activated caspase-3 and triggered gasdermin E(GSDME)- dependent pyroptosis in TNBC cells. Thus, VALD-3 treatment initiated the ROS/JNK/Bax-mitochondrial apoptosis pathway, leading to caspase-3 activation and GSDME cleavage, thereby executing pyroptosis. These findings suggest that GSDME-dependent pyroptosis is a novel mechanism by which VALD-3 eradicates cancer cells and offer new insights into potential clinical applications for anticancer therapies.
Correlation Between SGK1 Expression Level and Multiple Myeloma Progression After Autologous Hematopoietic Stem Cell Transplantation.
Fan T, Guo C, Zhang Y … +3 more , Yao J, Yu Y, Wang X
Biochem Genet · 2026 Jul · PMID 42384356 · Publisher ↗
To explore the correlation between serum and glucocorticoid inducible kinase-1 (SGK1) expression levels and the multiple myeloma (MM) progression in patients after autologous stem cell transplantation (ASCT). A total of...
To explore the correlation between serum and glucocorticoid inducible kinase-1 (SGK1) expression levels and the multiple myeloma (MM) progression in patients after autologous stem cell transplantation (ASCT). A total of 100 MM patients who received ASCT in the Hematology Department of our hospital during January 2020 to December 2022 were selected as the research subjects. The mRNA level of SGK1 was detected by RT-PCR. Taking the median relative expression level of SGK1 mRNA (2.15) as the critical value, these subjects were divided into SGK1 high expression group (SGK1 mRNA ≥ 2.15, n = 43) and SGK1 low expression group (SGK1 mRNA < 2.15, n = 57). The expression level of SGK1 was detected by IHC. The correlation was analyzed by Spearman correlation coefficient. The survival curve drawn through Kaplan-Meier method was further verified using Log-rank test. Cox proportional hazard regression model was used for multivariate analysis to screen independent risk factors. The receiver's working characteristic (ROC) curve was drawn to evaluate the predictive value. The H-Score was significantly higher in the SGK1 high expression group (8.52 ± 2.13) than the low expression group (3.27 ± 1.68) (t = 11.240, P < 0.001). After induction therapy, SGK1 high expression group had much lower proportion of achieving complete remission (CR), and markedly higher serum levels of β2-MG and LDH than SGK1 low expression group (P < 0.05). The expression of SGK1 in patients with partial remission (PR) was significantly higher than those with CR and very good partial remission (VGPR) (P < 0.01). Median TTP, median PFS and median OS were significantly lower in SGK1 high expression group than the SGK1 low expression group (Log-rank P < 0.01). Three months after transplantation, the positive rate of Minimal residual disease (MRD) was 48.84% (21/43) in SGK1 high expression group and 22.81% (13/57) in SGK1 low expression group (P < 0.01). The expression level of SGK1 was positively correlated with serum β2-MG (r = 0.452, P < 0.01), LDH (r = 0.388, P < 0.01), the proportion of plasma cells in bone marrow (r = 0.321, P < 0.01), and pre-transplant remission status (CR = 1, VGPR = 2, PR = 3; r = 0.413, P < 0.01), but negatively correlated with PFS (r= - 0.527, P < 0.01) and OS (r= - 0.482, P < 0.01). High SGK1 expression, serum β2-MG, and positive LDH and MRD were independent risk factors (P < 0.05). The ROC curve analysis of predicting disease progression after transplantation based on the relative expression level of SGK1 mRNA showed the area under the curve (AUC) of 0.883 (95% CI: 0.785-0.934), an optimal cutoff value of 2.18, a sensitivity of 94.32%, and a specificity of 73.63%. High expression of SGK1 was an independent risk factor for disease progression after ASCT in MM patients, which was closely related to the short survival time and high MRD positive rate. The expression level of SGK1 had a certain predictive effect on the disease progression after transplantation.
Decoding Genetic Risk Factors in Recurrent Pregnancy Loss: An Integrative Chromosomal and Bioinformatics Approach.
Mishra S, Ashish A, Rai S … +2 more , Yadav AK, Singh R
Biochem Genet · 2026 Jun · PMID 42374000 · Publisher ↗
Recurrent pregnancy loss (RPL) is characterized by two or more consecutive pregnancy losses, often associated with genetic, immunological, endocrine, and anatomical abnormalities. Among these, chromosomal abnormalities,...
Recurrent pregnancy loss (RPL) is characterized by two or more consecutive pregnancy losses, often associated with genetic, immunological, endocrine, and anatomical abnormalities. Among these, chromosomal abnormalities, including aneuploidies and submicroscopic copy number variations (CNVs), play a critical role in adverse pregnancy outcomes. A total of 125 fetal specimens were collected, of which 118 were included after applying predefined exclusion criteria. DNA isolated from products of conception and fetal tissues was subjected to quantitative fluorescent PCR (QF-PCR) for rapid aneuploidy screening. A subset of 30 samples with selected QF-PCR outcomes underwent array comparative genomic hybridization (aCGH). Identified CNVs were interpreted according to ACMG/ClinGen guidelines, followed by bioinformatics analyses using FunRich, WebGestalt, KEGG, and STRING to explore functional annotations and pathway enrichment. Among 118 samples, QF-PCR identified aneuploidy in 36 cases (30.5%), including monosomy (n = 20) and trisomy (n = 16), while 82 cases were reported as normal. Maternal age showed a significant association with chromosomal abnormalities (p < 0.05), and a weak negative correlation was observed between gestational age and aneuploidy risk (r = - 0.238, p = 0.008855). In the aCGH cohort (n = 30), clinically relevant CNVs were identified, including pathogenic and likely pathogenic variants, as well as variants of uncertain significance (VOUS). Notably, genes such as CFHR3, TNFRSF4, UGT2B17, CD24, MSR1, and the PSG gene family were implicated. Functional enrichment analysis revealed involvement in immune-inflammatory pathways, endocrine regulation, lipid metabolism, extracellular matrix remodeling, and placental development. This study demonstrates the enhanced diagnostic utility of combining aCGH with QF-PCR for identifying chromosomal abnormalities in RPL. However, the observed associations between CNVs and biological pathways are exploratory in nature and require validation in larger, well-powered cohorts.
Chromosome-Level Genome Assembly of the Sea Urchin Glyptocidaris crenularis and Sex Chromosome Identification.
Wang Q, Sun W, Zhai Y … +7 more , Wang Y, Li X, Ji H, Yu J, Gao R, Song Z, Zhang Q
Biochem Genet · 2026 Jun · PMID 42371287 · Publisher ↗
The economic importance of the sea urchin Glyptocidaris crenularis drives the need to elucidate the genetic mechanisms controlling its sex differentiation and development, a key step for enabling targeted genetic improve...
The economic importance of the sea urchin Glyptocidaris crenularis drives the need to elucidate the genetic mechanisms controlling its sex differentiation and development, a key step for enabling targeted genetic improvement. This study presents a chromosome-scale genome assembly for G. crenularis characterized by 22 chromosome-length scaffolds and a total length of 787.45 Mb. The phylogenetic tree revealed that G. crenularis diverged early among sea urchins. Synteny analysis among species suggested that superscaffold 10 might be the sex chromosome. Subsequent transcriptomic profiling further revealed 273 genes (298 transcripts) on chromosome 10 whose expression differed significantly between testis and ovary tissues. The genomic resources established in this study provide a foundation for investigating the population genetics, evolution, and functional mechanisms of this species, while the identified sex chromosomes and candidate genes pave the way for elucidating the molecular basis of sex determination in sea urchins.
Genetic Diversity and Population Structure of 72 Turkish Ficus carica (L.) Genotypes Assessed Using SCoT Markers.
Sarıkaya MF, Nadeem MA, Qureshi SA … +8 more , Bedir M, Tatar M, Ali A, Altaf MT, Uçer VA, Kökten K, Aglar E, Baloch FS
Biochem Genet · 2026 Jun · PMID 42348125 · Publisher ↗
Ficus carica L. is an economically important fruit crop widely cultivated in the Mediterranean region. In this study, genetic diversity and population structure were investigated in 72 F. carica genotypes collected from...
Ficus carica L. is an economically important fruit crop widely cultivated in the Mediterranean region. In this study, genetic diversity and population structure were investigated in 72 F. carica genotypes collected from the Derecik and Çukurca regions of Hakkâri province, Türkiye, using 15 highly polymorphic Start Codon Targeted (SCoT) markers. A total of 481 amplification bands were obtained, of which 475 were polymorphic, resulting in a high average polymorphism rate of 98.60%. Genetic diversity indices indicated substantial variation among the genotypes, with a mean effective number of alleles of 1.53, gene diversity of 0.31, and Shannon information index of 0.47. The average genetic distance among genotypes was 0.37, with the highest pairwise distance (0.721) observed between genotypes HC4 and HD7. Analysis of molecular variance (AMOVA) revealed that most genetic variation was distributed within populations (93%), whereas only 7% was among populations. Bayesian STRUCTURE analysis identified two distinct genetic clusters corresponding largely to geographic origin, with 22 genotypes (30.56%) classified as admixed based on a membership coefficient threshold of < 0.70. Principal coordinate analysis (PcoA) clearly separated genotypes according to their sampling locations, where Axis 1 and Axis 2 explained 24.31% and 15.07% of the total genetic variation, respectively. Overall, these findings demonstrate the effectiveness of SCoT markers in assessing genetic diversity and population structure in F. carica germplasm from southeastern Türkiye. Future studies should use codominant markers (SSRs and SNPs) expand geographic sampling, and adopt open data repositories to enhance conservation and breeding strategies.
A Splice-Site Variant in ACY1 Associated with Congenital Hearing Loss: Clinical, Biochemical, and Zebrafish Functional Evidence.
Yu S, Xu Z, Wang H … +8 more , Chen L, Hu SW, Zhang Y, Lyu H, Wu H, Wu M, Shu Y, Chen W
Biochem Genet · 2026 Jun · PMID 42322530 · Publisher ↗
Variants in the aminoacylase 1 (ACY1) gene are associated with diverse clinical phenotypes, but their roles in hearing loss remain unclear. This study aimed to investigate the potential role of ACY1 in hearing loss. Exom...
Variants in the aminoacylase 1 (ACY1) gene are associated with diverse clinical phenotypes, but their roles in hearing loss remain unclear. This study aimed to investigate the potential role of ACY1 in hearing loss. Exome sequencing was performed on 396 patients with sensorineural hearing loss. We identified a homozygous splicing variant, c.1063-1G>A, in ACY1 as a plausible candidate variant in a 5-year-old girl with congenital hearing loss and normal developmental milestones over a 4-year follow-up. Functional assays, including urinary organic acid analysis and aminoacylase 1 enzyme activity testing in Epstein-Barr virus (EBV)-transformed lymphoblasts, confirmed aminoacylase 1 deficiency in the patient. In vitro splicing assays showed that the c.1063-1G>A variant activated a cryptic splice site, causing aberrant splicing, a frameshift, and a premature stop codon. A zebrafish model with morpholino-mediated acy1 knockdown revealed a significant reduction in hair cells and impaired auditory function, which were effectively rescued by wild-type but not mutant human ACY1 mRNA. Furthermore, transcriptomic profiling of zebrafish auditory hair cells, combining fluorescence-activated cell sorting (FACS) with RNA sequencing, revealed downregulation of critical inner ear development genes, including gfi1ab and atoh1a/b, which was validated by RT-qPCR. These results provide clinical and experimental evidence supporting the functional impact of the ACY1 c.1063-1G>A variant and its potential involvement in congenital hearing loss. Our findings support ACY1 as a candidate gene for hereditary hearing impairment, although additional unrelated patients and independent validation are needed to further establish the gene-disease relationship.
Replication Study of ENPP1 Variants and Haplotypes Associated with Severe Obesity in a Greek Adult Population.
Rouskas K, Meyre D, Lobbens S … +3 more , Papazoglou D, Kouvatsi A, Froguel P
Biochem Genet · 2026 Jun · PMID 42322529 · Publisher ↗
The ENPP1 (Ectonucleotide pyrophosphatase/phosphodiesterase 1) gene, encoding a protein that negatively modulates insulin receptor activation, remains relatively understudied in obesity genetics. K121Q (rs1044498; chr6:1...
The ENPP1 (Ectonucleotide pyrophosphatase/phosphodiesterase 1) gene, encoding a protein that negatively modulates insulin receptor activation, remains relatively understudied in obesity genetics. K121Q (rs1044498; chr6:132,172,368: A > C) and other ENPP1 genetic variants (rs1799774; chr6:132,203,471: insT> delT and rs7754561; chr6:132,212,694: A > G), as well as the risk haplotype Q-delT-G have been investigated for their association with obesity risk mostly in populations from Central and Northern Europe, yielding controversial findings. Given the significance of reproducibility in genetic association studies and the scarcity of data from Southern Europe, we performed a case-control replication study to test the hypothesis that ENPP1 variants and haplotypes are associated with severe obesity in the underexplored and high-risk Greek population. A total of 979 Greek individuals (mean age: 47.6 ± 12.5years old), including 510 adults with severe obesity (BMI≥35Kg/m) and 469 normal-weight (18.5 < BMI<25Kg/m) controls, were studied. Three ENPP1 variants (rs1044498, rs1799774 and rs7754561) were genotyped using the TaqMan allelic discrimination assay. Logistic regression was applied to detect association of variants with obesity. Linkage disequilibrium among the three variants was assessed, and haplotype frequencies were compared between groups. The three variants did not exhibit any association with adult severe obesity. The three variants were in partial linkage disequilibrium (r ≤ 0.43). ENPP1 haplotype distribution differed significantly between normal-weight individuals and those with adult severe obesity (likelihood ratio x = 13.38, P = 0.020), with the Q-delT-G haplotype found to be present exclusively in individuals with adult severe obesity (frequency 3.3%) and to be associated with adult severe obesity (x = 5.66, P = 0.017; reference haplotype K-InsT-A, consisting of the three major alleles of the three variants). Our replication findings contribute novel evidence regarding the genetic architecture of adult severe obesity in a Southern-European population, however larger studies are necessary to validate these results.
Exercise-Driven NRF2 Activation as a Systemic Neuroprotective Strategy: Integrating Redox Biology, Muscle-Brain Crosstalk, and Therapeutic Targeting in Neurodegeneration.
Deng P, Deng W, Wang L … +2 more , Ye W, Li S
Biochem Genet · 2026 Jun · PMID 42313222 · Publisher ↗
Neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's diseases, are characterized by progressive neuronal dysfunction and loss. Recent evidence highlights the importance of the nuclear factor e...
Neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's diseases, are characterized by progressive neuronal dysfunction and loss. Recent evidence highlights the importance of the nuclear factor erythroid 2-related factor 2 (NRF2) pathway, a key regulator of cellular defense mechanisms, in maintaining neuronal health and function. A narrative literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar to identify relevant experimental, clinical, and review studies on NRF2 signaling, physical exercise, oxidative stress, muscle-brain crosstalk, and neurodegenerative diseases. Keywords included "NRF2", "Nrf2/Keap1/ARE", "physical exercise", "exercise-induced oxidative stress", "myokines", "exerkines", "Alzheimer's disease", "Parkinson's disease", "Huntington's disease", and "amyotrophic lateral sclerosis". NRF2 modulates the expression of a variety of antioxidant and cytoprotective genes, contributing to the protection of neurons against oxidative stress, inflammation, and protein aggregation, processes central to the pathogenesis of neurodegenerative diseases. Additionally, physical activity has been identified as a powerful modulator of NRF2 activation, with exercise offering neuroprotective effects through the induction of NRF2-mediated pathways. This review explores the interplay between NRF2 activation and physical exercise in the context of neurodegenerative diseases, detailing the molecular mechanisms by which exercise influences NRF2 activity to combat cellular damage and enhance neuroprotection. We discuss the therapeutic potential of combining exercise regimens with NRF2-targeted therapies, highlighting the promise of this dual approach in slowing disease progression, improving cognitive function, and enhancing quality of life in affected individuals. Furthermore, we examine the challenges and future directions for clinical implementation, including optimal exercise protocols and the development of NRF2-based pharmacological interventions. This review underscores the importance of NRF2 as a central mediator of neuroprotection and the therapeutic promise of physical activity in the management of neurodegenerative diseases.
Splicing Alterations Associated with Multiple Homozygous TNXB Variants in a Patient with Suspected Classical-Like Ehlers-Danlos Syndrome.
Imanaka B, Hasegawa Y, Kawato K … +5 more , Kimoto Y, Oda I, Okamoto N, Saigoh K, Nakama M
Biochem Genet · 2026 Jun · PMID 42295573 · Publisher ↗
Ehlers-Danlos syndrome (EDS) comprises a heterogeneous group of heritable connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Classical-like EDS (clEDS) is typ...
Ehlers-Danlos syndrome (EDS) comprises a heterogeneous group of heritable connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Classical-like EDS (clEDS) is typically associated with pathogenic biallelic variants in TNXB. The patient showed generalized joint hypermobility involving the knees, fingers, elbows, and feet, along with soft, pliable skin. She had a history of three dislocations of the right elbow and one dislocation of the left elbow. She also reported orthostatic dizziness and chronic constipation, suggesting possible autonomic nervous system involvement. Cardiovascular assessment detected mild mitral valve regurgitation. Based on these findings, hypermobility syndrome or EDS was suspected, and gene panel testing was conducted for classical and pseudo-classical EDS. The patient was found to be homozygous for multiple TNXB (NM_001365276.2) variants, including c.11,925 + 6 C > G, c.12,156 C > G (p. Arg4052=), c.12,210 + 5G > A, c.12,210 + 39dup, and c.12,210 + 43T > G, and also carried a mosaic variant c.8012 C > T (p. Ala2671Val). To investigate the potential effects of these variants on splicing, RT-PCR using peripheral blood RNA and in vitro minigene splicing assays were performed. Analysis of the patient-derived cDNA and cDNA derived from mutant minigenes revealed alternative splicing leading to intron 40 retention alongside the normal transcript. Intron 40 retention was more pronounced with multiple variants and was most prominently associated with c.12,210 + 5G > A in the minigene assays. These results suggest that c.12,210 + 5G > A can influence TNXB splicing, generating in-frame transcripts. The aberrant transcripts are predicted to affect the fibrinogen C-terminal domain. Although the clinical significance of these variants remains uncertain, these findings highlight the importance of integrating population frequency data, clinical assessment, and functional analyses when interpreting uncertain TNXB variants in patients with suspected clEDS.
Comparative Analysis of Stemness and Differentiation Gene Expression in Mesenchymal Stem Cells from Permanent and Deciduous Teeth: An In Vitro Study to Evaluate Implications for Regenerative Dentistry.
Noorbakhsh SAA, Pourmohammadi-Nejad F, Pirsadeghi A … +1 more , Yousefi-Ahmadipour A
Biochem Genet · 2026 Jun · PMID 42283766 · Publisher ↗
Dental pulp is a valuable source of mesenchymal stem cells (MSCs), offering significant promise for cell therapy and regenerative medicine, particularly in treating oral and dental conditions. For clinical translation, u...
Dental pulp is a valuable source of mesenchymal stem cells (MSCs), offering significant promise for cell therapy and regenerative medicine, particularly in treating oral and dental conditions. For clinical translation, understanding which dental stem cell source provides superior proliferative and differentiation capacity for specific tissue regeneration (bone vs. dentin) is essential. This study aimed to compare the gene expression profiles and osteogenic potential of MSCs derived from permanent (DPSCs) and deciduous (SHED) teeth. DPSCs and SHED were isolated and characterized using flow cytometry. Their differentiation potential into bone and fat cells was assessed, along with colony formation, doubling time (DT), cell viability, alkaline phosphatase (ALP) activity, and the expression of stemness genes (SOX2, OCT4, NANOG) and differentiation genes (OCN, DSPP, AMBN, SPARC, IBSP). SHEDs showed higher colony formation (33.66 vs. 28.33) and shorter doubling time (33.13 h vs. 39.25 h) compared to DPSCs. Importantly, SHEDs exhibited significantly higher ALP activity after osteogenic induction, confirming their superior early osteogenic differentiation potential. SHEDs also expressed stemness genes (OCT4, NANOG, SOX2) and osteogenic markers (AMBN, OCN) at higher levels, while DPSCs showed higher expression of odontogenic markers (DSPP, SPARC, IBSP). Overall, SHEDs in this study showed greater proliferative capacity, faster doubling times, and enhanced early osteogenic potential compared to DPSCs, whereas DPSCs showed stronger odontogenic differentiation potential. These findings suggest that SHEDs may be more suitable for bone and enamel-like tissue regeneration, while DPSCs are better suited for dentin-pulp complex repair, providing a rationale for stem cell selection in regenerative dentistry.
Fisetin Modulates Chemoresistance-Associated miR-21, miR-181a, miR-203, miR-101 and miR-381 in Capecitabine-Resistant HT29 Colorectal Cancer Cells.
Kanlı Z, Eyüboğlu İP, Arga KY … +3 more , Aydın B, Erzik C, Cabadak H
Biochem Genet · 2026 Jun · PMID 42277456 · Publisher ↗
Capecitabine is a key component of colorectal cancer (CRC) chemotherapy; however, acquired resistance markedly limits its efficacy. MicroRNAs (miRNAs) are central regulators of drug response, and the flavonoid fisetin ha...
Capecitabine is a key component of colorectal cancer (CRC) chemotherapy; however, acquired resistance markedly limits its efficacy. MicroRNAs (miRNAs) are central regulators of drug response, and the flavonoid fisetin has been reported to exert anti-tumor and chemosensitizing effects. Here, we investigated whether fisetin modulates the expression of chemoresistance-associated miRNAs in a capecitabine-resistant CRC cell model. Candidate miRNAs were prioritized from the publicly available dataset GSE30894 using differential expression analysis, which identified miR-21, miR-181a, miR-203, miR-101, and miR-381 as differentially expressed between sensitive and resistant colorectal cancer cells. These miRNAs were quantified by RT-qPCR in parental HT29 and capecitabine-resistant HT29 (CR/HT29) cells under basal conditions and after 24-h exposure to capecitabine (40 µM), fisetin (120 µM), or the combination. Nuclear morphology was assessed by DAPI staining. At baseline, CR/HT29 cells showed lower expression of miR-381, miR-21, miR-203, and miR-101 and a trend towards higher miR-181a compared with parental HT29 cells. Treatment with capecitabine, fisetin, or their combination differentially modulated these miRNAs in the two cell lines. In both parental and resistant cells, fisetin-containing regimens reduced miR-21, while in CR/HT29 cells, fisetin significantly decreased miR-181a expression compared with fisetin-treated parental cells. Fisetin and fisetin + capecitabine also altered miR-203 and miR-101 levels, with a more pronounced suppression in HT29 than in CR/HT29 cells. These changes were accompanied by marked morphological alterations in resistant cells. Fisetin modulates chemoresistance-associated miRNAs in colorectal cancer, particularly in capecitabine-resistant HT29 cells, suggesting a chemosensitizing adjuvant role and offering an in vitro basis for in vivo studies.
HILPDA, Regulated by WTAP in an m6A-Dependent Manner, Enhances Osteosarcoma Development by Inhibiting Ferroptosis and Promoting Glycolysis.
Jing Y, Zhang G, Sun C … +6 more , Pan Y, Tuo J, Li Z, Jiang C, Qiu Z, Lou Q
Biochem Genet · 2026 Jun · PMID 42274843 · Publisher ↗
Osteosarcoma (OS) is the most common primary malignant bone cancer. Hypoxia-inducible lipid droplet-associated protein (HILPDA) promotes tumor growth, migration, and ferroptosis resistance in OS. However, the oncogenic m...
Osteosarcoma (OS) is the most common primary malignant bone cancer. Hypoxia-inducible lipid droplet-associated protein (HILPDA) promotes tumor growth, migration, and ferroptosis resistance in OS. However, the oncogenic mechanisms of HILPDA in OS are largely unexplored. Glycolytic activity was assessed by measuring glucose uptake and lactate release. Ferroptosis was evaluated by measuring ROS, MDA, Fe, and total iron contents. Cell proliferation was assessed via EdU incorporation assay, and tube formation ability was analyzed. Animal experiments were used to test the function in vivo. Expression analysis was performed using quantitative PCR, immunoblotting, and immunohistochemistry. The regulation of Wilms' tumor 1-associating protein (WTAP) in HILPDA was detected by methylated RNA immunoprecipitation (MeRIP) assay. HILPDA and WTAP were upregulated in OS tissues. Overexpression of HILPDA or WTAP was associated with poor prognosis in OS patients. HILPDA deficiency impaired OS cell proliferation and glycolysis while promoting ferroptosis, concurrently attenuating HUVEC tube formation in vitro. Moreover, HILPDA depletion constrained the in vivo growth of HOS OS xenografts. Mechanistically, WTAP regulated HILPDA expression through an m6A-dependent manner. Additionally, HILPDA re-expression reversed sh-WTAP-mediated alterations in OS cell glycolysis and ferroptosis and HUVEC tube formation. Our findings identify the WTAP/HILPDA axis as a key regulator of OS development through coordinated control of glycolysis, ferroptosis, and angiogenesis, offering new avenues for multi-targeted therapeutic intervention in OS.
COVID-19 as a Modifier of Genetically Determined Coagulation Phenotype: Implications for Precision Risk Stratification After Infection.
Perevezentsev OA, Mamedov IS, Burtsev DV
Biochem Genet · 2026 Jun · PMID 42260034 · Publisher ↗
Persistent endothelial dysfunction and coagulation abnormalities are increasingly recognized as central components of post-COVID syndrome. However, substantial interindividual variability in long-term coagulation biomark...
Persistent endothelial dysfunction and coagulation abnormalities are increasingly recognized as central components of post-COVID syndrome. However, substantial interindividual variability in long-term coagulation biomarkers suggests the presence of genetically determined susceptibility factors capable of modulating post-infectious thromboinflammatory responses. To determine whether common prothrombotic genetic variants modify long-term D-dimer and INR levels after COVID-19 and to assess their value for precision risk stratification. A controlled observational cohort study included 504 adults aged 18-50 years examined more than two years after PCR-confirmed COVID-19 and 270 control individuals without clinically significant SARS-CoV-2 infection. Genotyping of F2 c.20210G > A, F5 c.1691G > A (Factor V Leiden), and MTHFR c.C677T was performed using real-time PCR. D-dimer and international normalized ratio (INR) were measured monthly for 12 months and averaged. Log-transformed D-dimer was analyzed using multivariable linear regression with interaction terms. All three variants were independent predictors of D-dimer. In adjusted models, F2 GA (+ 31%), F5 GA (+ 37%), MTHFR CT (+ 34%), and MTHFR TT (+ 67%) were associated with higher D-dimer levels (all p < 0.001). Significant amplification of genetic effects was observed in post-COVID individuals (Group × Genotype interaction p < 0.01). INR showed no genotype association. COVID-19 acts as a long-term modifier of inherited thrombophilia phenotypes. Incorporating genetic profiling into post-COVID evaluation may enable precision identification of individuals at risk for persistent hypercoagulability.
Promoter Methylation of HOXA5 and NDRG2 in Multiple Myeloma Patients with Renal Impairment.
Haroun RA, Elsaid DS, Al-Dosoky MA … +3 more , Elbedewy TA, Gamal-Eldin SM, Keshk RA
Biochem Genet · 2026 Jun · PMID 42258087 · Publisher ↗
Renal impairment (RI) is frequently caused by multiple myeloma (MM), which makes clinical care more difficult if renal function deteriorates or renal failure develops. Thus, in this investigation, we looked at the relati...
Renal impairment (RI) is frequently caused by multiple myeloma (MM), which makes clinical care more difficult if renal function deteriorates or renal failure develops. Thus, in this investigation, we looked at the relationship between HOXA5&NDRG2 promoter methylation in MM patients and evaluated their prognostic potential in predicting RI risk in MM patients. This study included 60 control volunteers and 120 MM patients. The promoter methylations of HOXA5&NDRG2 were quantitatively evaluated by real-time PCR (qPCR) after the extraction of gDNA from whole blood and then treated with bisulfite. The promoter methylation percentages of HOXA5&NDRG2 were significantly increased in MM patients (77.16 ± 2.43&45.49 ± 2.16;p < 0.05) when compared to controls (4.47 ± 0.61&3.33 ± 0.31,respectively), in stage II&III patients when compared to stage I patients and in patients with age ≥ 60 years when compared to patients with age < 60 years. While only the methylation percentage of NDRG2 promoter was significantly increased in MM patients with RI (53.61 ± 3.21,p < 0.05) when compared to MM patients without RI (37.37 ± 2.04). Results obtained from ROC curve revealed that both HOXA5&NDRG2 promoter methylation were good diagnostic tools for MM. The NDRG2 promoter methylation was good prognostic biomarker could predict renal while HOXA5 promoter in the prediction of MM staging. The Kaplan-Meier survival test showed that patients with higher HOXA5&NDRG2 promoter methylation had a shorter OS and a worse prognosis. Only NDRG2 promoter hypermethylation was significantly associated with the risk of RI development in MM patients. HOXA5&NDRG2 promoter hypermethylation may have roles in the molecular etiology of MM and could be used as a treatment regimen.
Hedyotis diffusa Willd-Scutellaria barbata D.Don Suppresses Colorectal Cancer Liver Metastasis by Targeting hsa_circ_0039933-Mediated Epithelial-Mesenchymal Transition.
Yuan S, Li S, Chen C
Biochem Genet · 2026 Jun · PMID 42258086 · Publisher ↗
Colorectal cancer (CRC) liver metastasis remains a major cause of mortality, necessitating novel therapeutic strategies. Hedyotis diffusa Willd -Scutellaria barbata D.Don (HD-SB), a traditional Chinese herbal formulation...
Colorectal cancer (CRC) liver metastasis remains a major cause of mortality, necessitating novel therapeutic strategies. Hedyotis diffusa Willd -Scutellaria barbata D.Don (HD-SB), a traditional Chinese herbal formulation, has demonstrated anti-tumor potential. However, its mechanism in CRC metastasis, particularly through the regulation of circular RNAs, remains unexplored. A CRC liver metastasis model was established in Balb/c nude mice via intrasplenic injection of HCT-15 cells. Mice received HD-SB treatment. Hematoxylin-eosin staining, Masson staining, and immunohistochemistry (Ki67 and Cytokeratin 19 [CK19]) were carried out to observe pathologic changes in CRC liver metastases. In vitro, HCT-15 cells were treated with tumor necrosis factor-α (TNF-α) to induce metastasis. hsa_circ_0039933 was knocked down and overexpressed in vitro. Transwell, wound healing, EdU, and cell counting kit-8 assays were employed to assess cell invasion, migration and proliferation, respectively. The levels of epithelial-mesenchymal transition (EMT) markers were evaluated by quantitative real-time polymerase chain reaction and western blot. HD-SB treatment dose-dependently reduced hepatic tumor nodules, fibrosis, Ki67 and CK19 expression in vivo, with high-dose HD-SB showing superior efficacy. EMT reverse (upregulated E-cadherin, downregulated N-cadherin/Vimentin) and hsa_circ_0039933 suppression were observed in HD-SB treated CRC mouse. In vitro, HD-SB attenuated TNF-α-induced proliferation, migration, and invasion, synergizing with hsa_circ_0039933 knockdown to suppress EMT and metastatic phenotypes. Conversely, hsa_circ_0039933 overexpression exacerbated TNF-α-driven aggressiveness, which was effectively counteracted by HD-SB. Collectively, HD-SB inhibits CRC liver metastasis by targeting hsa_circ_0039933 and modulating EMT. These findings highlight HD-SB as a promising circRNA-directed therapeutic agent for metastatic CRC.
Lactate as a Signaling Molecule in the Tumor Microenvironment: Implications for Cancer Progression.
Kamil SS, Al-Bdery ASJ, Al-Marzoqi AH … +2 more , Abdulabbas HT, Shakir AJ
Biochem Genet · 2026 Jun · PMID 42258085 · Publisher ↗
Aerobic glycolysis is a process commonly utilized by tumor cells to produce excessive lactate, acidification of the extracellular milieu and promoting tumor progression. Lactate plays its roles as a metabolic intermediat...
Aerobic glycolysis is a process commonly utilized by tumor cells to produce excessive lactate, acidification of the extracellular milieu and promoting tumor progression. Lactate plays its roles as a metabolic intermediate and as a signaling molecule in the tumor microenvironment (TME). In this literature review, we first describe how cancer cells alter their metabolism, focusing on the Warburg effect, LDHA-mediated lactate catalysis, and MCT1/4's role in its removal. Next, we explain GPR81-mediated signal transduction and inhibition of HIF-1α and NF-κB degradation, which connects metabolism to oncogenic signaling pathways. We discuss lactate-driven histone lactylation as an epigenetic process that enhances gene expression for growth, angiogenesis, and immune evasion. We also examine lactate effects on Immune cells by inhibition of CD8 + T and NK cells, macrophage polarization toward the M2 phenotype, and inhibition of dendritic cell (DC) maturation. Lactate shuttling between cancer-associated fibroblasts and tumor cells promotes metabolic symbiosis and therapy resistance. Lastly, this review examines treatment options targeting LDH and MCTs, either on their own or in combination with immunotherapy. We also discuss challenges including compensatory pathway activation and off-target effects. Understanding the mechanisms of lactate 's effects on the TME facilitates the development of more effective metabolic and immunometabolic cancer treatments. From a clinical perspective, targeting lactate metabolism through LDHA inhibitors and MCT blockers, alone or combined with immune checkpoint inhibitors, represents a promising strategy to recondition the immunosuppressive TME and improve therapeutic outcomes. However, metabolic plasticity, pathway redundancy, and insufficient tumor selectivity remain significant translational challenges that warrant further investigation.
Epirubicin-Induced Upregulation of miR-143-3p and miR-145 Enhances Cytotoxicity in MCF-7, MDA-MB-231, and BT-474 Breast Cancer Cell Lines.
Rajabi M, Mohammadi NG, Mombeyni M … +1 more , Andouhjerdi RB
Biochem Genet · 2026 Jun · PMID 42258084 · Publisher ↗
Drug resistance poses a significant challenge to effective breast cancer chemotherapy. This study investigated the regulatory effects of Epirubicin on miR-143-3p and miR-145 expression in BT-474, MCF-7, and MDA-MB-231 br...
Drug resistance poses a significant challenge to effective breast cancer chemotherapy. This study investigated the regulatory effects of Epirubicin on miR-143-3p and miR-145 expression in BT-474, MCF-7, and MDA-MB-231 breast cancer cell lines. These miRNAs, known as tumor suppressors, are often downregulated in breast carcinoma, correlating with poorer prognosis. Cells were treated with Epirubicin, and miR-143-3p and miR-145 expression was quantified via qRT-PCR. Epirubicin IC values were 0.42 µg/mL (MCF-7), 2.94 µg/mL (MDA-MB-231), and 0.86 µg/mL (BT-474) after 48 h, demonstrating dose- and time-dependent cytotoxicity. Treatment significantly upregulated miR-143-3p and miR-145 expression, with MCF7 cells showing a 3.5-fold increase in miR-145 (p < 0.01) and a 2.8-fold increase in miR-143-3p (p < 0.05) compared to controls. Cell viability decreased by up to 70% at 6 µg/mL Epirubicin in MCF-7 cells, with apoptosis rates rising to 8.65% (MCF-7) and 9.75% (MDA-MB-231) after 24 h (p < 0.01). Colony formation was reduced by 60-80% across cell lines (p < 0.001), and wound closure was inhibited by 40-50% in MDA-MB-231 cells at 24 h (p < 0.0001). These findings suggest that Epirubicin enhances therapeutic efficacy by upregulating miR-143-3p and miR-145, potentially mitigating drug resistance. This highlights their potential as therapeutic targets for improving outcomes in resistant breast cancer subtypes.
Vitamin D Supplementation Modulates Base Excision Repair (BER) Machinery in Systemic Sclerosis: A Prospective Longitudinal Study.
Dal-Bekar NE, Birdogan A, Islekel GH … +2 more , Birlik AM, Akdogan G
Biochem Genet · 2026 Jun · PMID 42258083 · Publisher ↗
Systemic sclerosis (SSc) is a chronic, autoimmune, fibrotic disorder involving immune dysregulation, vascular abnormalities and progressive fibrosis. Although oxidative stress and defective DNA repair have been implicate...
Systemic sclerosis (SSc) is a chronic, autoimmune, fibrotic disorder involving immune dysregulation, vascular abnormalities and progressive fibrosis. Although oxidative stress and defective DNA repair have been implicated in its pathogenesis, the impact of vitamin D on DNA repair pathways remains unclear. This study aimed to investigate the expression of DNA repair enzymes in SSc, explore their relationship with vitamin D status and assess the effects of vitamin D supplementation on the transcriptional expression of these enzymes. Peripheral blood samples were collected from 52 female patients with SSc and 31 age-matched healthy controls (HCs). Gene expression levels of base excision repair (BER) enzymes (APE1 and OGG1) and nucleotide excision repair (NER) enzymes (XPA and XPC) were analyzed. Serum vitamin D levels were measured and correlated with disease activity scores. In a prospective arm of the study, patients received six months of vitamin D supplementation and their DNA repair capacity was evaluated pre- and post-intervention. Baseline expression of APE1 and OGG1 was significantly lower in SSc patients than in HCs, whereas expression of the NER genes remained unchanged, indicating selective impairment of the BER pathway. Vitamin D deficiency was prevalent in SSc and inversely correlated with disease severity. Supplementation significantly increased serum vitamin D levels and up-regulated APE1 and OGG1 expression; while NER genes remained unaffected. These findings are consistent with evidence of elevated oxidative DNA lesions in SSc and support a mechanistic link between BER activity and the repair of oxidative DNA damage. SSc patients exhibit reduced transcription of BER-specific enzymes associated with vitamin D deficiency andrestoration of vitamin D levels partially rescues BER enzyme expression. These findingshighlight a potentially modifiable axis linking micronutrient status, genomic stability and disease activity and provide a rationale for investigating vitamin D optimization as an adjunctive strategy to enhance DNA repair and potentially attenuate inflammatory and fibrotic processes in SSc.
Genomic and Molecular Interaction Analysis of NodD1 in a Novel Bradyrhizobium yuanmingense sp. B64 Isolate for Nodulation and Symbiosis of Legume Plants.
Aslan A, Simarmata R, Santosa D … +5 more , Widowati T, Lekatompessy S, Merrisa A, Bait M, Palar R
Biochem Genet · 2026 Jun · PMID 42252372 · Publisher ↗
Rhizobial bacteria are known for their ability to fix nitrogen for leguminous plants and their essential function for sustainable agriculture. This study characterizes the taxonomic status and functional potential of the...
Rhizobial bacteria are known for their ability to fix nitrogen for leguminous plants and their essential function for sustainable agriculture. This study characterizes the taxonomic status and functional potential of the Bradyrhizobium B64 isolate using integrated genomic and molecular approaches. The whole genome of the B64 isolate was sequenced via Illumina paired-end technology. Species delimitation was performed using average nucleotide identity (ANI) and digital DNA-DNA Hybridization (dDDH). The NodD1 protein structure was modeled using AlphaFold3 and validated by Ramachandran plot analysis. Molecular docking was then conducted to evaluate interactions between NodD1 and four signaling flavonoids: Apigenin, Daidzein, Genistein, and Naringenin. Genomic analysis revealed a maximum ANI of 94.4% and dDDH values between 51.4 and 62.4%. Since these values fall below the standard prokaryotic thresholds (ANI < 95%; dDDH < 70%), the B64 isolate is identified as a novel species. Physiological assays confirmed nitrogen fixation (1.97 ppm), IAA production (3.67 ppm), and phosphate solubilization (26.10 ppm). Structural validation showed 100% of NodD1 residues in allowed regions, ensuring high model reliability. Docking simulations demonstrated strong binding affinities across all flavonoids, with binding free energies ranging from - 8.8 to - 9.0 kcal/mol. Daidzein exhibited the highest thermodynamic stability (- 9.0 kcal/mol), whereas apigenin showed the most extensive residue interaction network. The B64 isolate is a novel Bradyrhizobium species with a high symbiotic capacity. The stable NodD1-flavonoid interactions provide a molecular basis for efficient nodulation, positioning B64 as a promising candidate for developing lipo-chitooligosaccharide (LCO)-based biofertilizers.
Carbapenem-Resistant Acinetobacter baumannii: Resistance, Virulence, and Possible Dissemination Between Different Hospitals in Western Iran.
Niknian M, Feizi K, Bakhshi B … +1 more , Derakhshan S
Biochem Genet · 2026 Jun · PMID 42252371 · Publisher ↗
The capacity for biofilm formation, along with the acquisition of antimicrobial resistance, could be the primary factors enhancing the persistence and spread of Acinetobacter baumannii (AB). We aimed to identify the tren...
The capacity for biofilm formation, along with the acquisition of antimicrobial resistance, could be the primary factors enhancing the persistence and spread of Acinetobacter baumannii (AB). We aimed to identify the trends in molecular epidemiology of AB isolated from western Iran. Ninety-nine pathogenic AB isolates were collected from patients in three major hospitals in Sanandaj and Kermanshah (the capitals of Kurdistan and Kermanshah provinces in western Iran, respectively) in one year. Isolates were tested for the presence of class D and B carbapenemases, integrons, and biofilm-associated genes, and their genetic diversity was initially investigated using enterobacterial repetitive intergenic consensus (ERIC) analysis, followed by multilocus sequence typing (MLST) and plasmid profiling. Of the 99 isolates, 91.9% showed resistance to carbapenems. The most common class D and class B carbapenemases were OXA-24-like and VIM type, respectively. The bap, bfmR, and ompA biofilm-related genes were present in all isolates. Class 1 integron was only identified in 10.1% of isolates and contained the sugar dehydrogenase gene cassette. By ERIC, Cluster C was found in three hospitals, and Clone A in two hospitals. By MLST, isolates in Cluster C and Clone A were assigned to ST78 and ST2125, respectively. Plasmid profiling of Cluster C and Clone A isolates showed similar plasmid profiles. Our research offers insights into the epidemiology of AB circulating in western Iran during recent years. The results may suggest a possible inter-hospital spread of these strains; however, further research is needed. We document for the first time the emergence of ST2125 and ST78 in Iran.
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