Biochemical Genetics[JOURNAL]
Sun
200 papers
Genome-Wide Identification and Expression Analysis of the NIN-LIKE Protein (NLP) Gene Family in Salvia Miltiorrhiza.
Hao S, Zhu R, Zhang H … +6 more , Wang Y, Zhao D, Guo M, Li Q, Wang L, Kai G
Biochem Genet · 2025 Nov · PMID 41236691 · Publisher ↗
NIN-like proteins (NLPs) are plant-specific transcription factors with a conserved RWP-RK domain that can bind to nitrate-responsive cis-elements (NREs) in target gene promoters. NLPs play essential roles in nitrogen upt...
NIN-like proteins (NLPs) are plant-specific transcription factors with a conserved RWP-RK domain that can bind to nitrate-responsive cis-elements (NREs) in target gene promoters. NLPs play essential roles in nitrogen uptake, transport, metabolism, and are also involved in nitrate signaling, root development, and secondary metabolism. Salvia miltiorrhiza is a medicinal plant valued for its roots and rhizomes. It mainly contains two types of active ingredients: tanshinones and salvianolic acids. Previous studies have shown that nitrogen availability significantly affects the growth of S. miltiorrhiza and the accumulation of its active ingredients, but the regulatory mechanism has not yet been fully elucidated. In this study, 11 SmNLPs were identified in the S. miltiorrhiza genome through bioinformatic analyses, and they were found to be distributed across eight chromosomes. Phylogenetic analysis grouped them into three subfamilies, with members in the same clade sharing similar gene structures and conserved domains. Promoter analysis revealed that SmNLPs harbor cis-acting elements involved in stress responses, hormone signaling, development, and light responses. Tissue-specific expression analysis of two-year-old S. miltiorrhiza plants showed that SmNLPs are broadly expressed in roots, stems, leaves, and flowers, exhibiting distinct tissue-specific patterns. Among them, most SmNLPs, particularly SmNLP3 and SmNLP8, were significantly upregulated in nitrogen-deprivation hairy roots. Co-expression analysis based on transcriptome data suggested that SmNLP3, SmNLP8, and SmNLP10 may be involved in the regulation of tanshinone and salvianolic acid biosynthesis. These findings provide new insights into the potential roles of NLPs in nitrogen response and secondary metabolism in S. miltiorrhiza, laying a foundation for future functional studies and metabolic engineering.
Mitogenomic Architecture of Mycetophylax conformis (Hymenoptera: Formicidae): Evidence for Conserved Gene Order and Strand Asymmetry in Myrmicinae.
Cardoso DC, de Lima Baldez BC, Vasconcelos HR … +2 more , Kalapothakis E, Cristiano MP
Biochem Genet · 2025 Nov · PMID 41236690 · Publisher ↗
Mitochondrial genomes are powerful tools for investigating the evolutionary dynamics and genetic diversity of social insects, particularly ants. Here, we present the complete mitochondrial genome of Mycetophylax conformi...
Mitochondrial genomes are powerful tools for investigating the evolutionary dynamics and genetic diversity of social insects, particularly ants. Here, we present the complete mitochondrial genome of Mycetophylax conformis, a psammophilous, fungus-farming ant endemic to the Atlantic coastal sand dunes of southeastern Brazil. The circular mitogenome is 16,455 base pairs long and includes the canonical 37 genes: 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), 2 ribosomal RNAs (rRNAs), and a control region (CR). Gene content and order are consistent with those of other Myrmicinae ants. The nucleotide composition is strongly biased toward adenine and thymine (A+T = 82.1%) and exhibits moderate strand asymmetries, with an AT-skew of - 0.111 and a GC-skew of - 0.171. No large intergenic spacers or atypical structural features were identified, suggesting a highly conserved genomic architecture. This newly assembled mitogenome enhances the representation of Neoattina in mitochondrial databases and provides a valuable reference for future evolutionary, ecological, and comparative genomic studies of fungus-farming ants.
Acute Myeloid Leukemia Patients with High-Risk Karyotypes Benefit from Decitabine in Combination with Modified CAG.
Liu P, Lu C, Sun Q … +6 more , Zhu Y, Zhao X, Li J, Qian S, Hong M, Liu W
Biochem Genet · 2025 Nov · PMID 41236689 · Publisher ↗
This study aims to investigate the genetic characteristics of Acute Myeloid Leukemia (AML) patients and identify which patients derive the greatest benefit from a low-intensity regimen of decitabine combined with modifie...
This study aims to investigate the genetic characteristics of Acute Myeloid Leukemia (AML) patients and identify which patients derive the greatest benefit from a low-intensity regimen of decitabine combined with modified Cytarabine + Aclarubicin + Granulocyte Colony-Stimulating Factor (D-CAG) or intensive chemotherapy (IA regimen). We retrospectively analyzed cytogenetic and molecular data of 331 newly diagnosed AML patients and examined the associations between genetic characteristics, risk status, treatment approaches, and clinical outcomes. The median follow-up duration was 45 months (range: 2-120 months). Patients receiving IA therapy achieved higher complete remission (CR) rates (79.3% vs. 66.4%, P < 0.05), while objective response rates (ORR) remained comparable between the two treatment arms. Both in the total cohort and among favorable-risk patients, the median overall survival (OS) was significantly reduced in the D-CAG group compared to the IA group (P < 0.05). For intermediate- and high-risk patients who had not undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT), median OS outcomes were comparable between the two treatment regimens. Patients harboring TET2 (Tet methylcytosine dioxygenase 2), NRAS (Neuroblastoma RAS viral oncogene homolog), or biallelic CEBPA mutations demonstrated superior OS in the IA group compared to the D-CAG group (P < 0.05). Notably, older patients with complex or monosomal karyotypes exhibited longer median OS than their younger counterparts (P < 0.05). In conclusion, D-CAG may represent a more suitable therapeutic option for AML patients with high-risk karyotypic profiles.
A Homozygous Mutation (c.241G > A, p.A81T) in the Calsequestrin-2 Causes Eye Defects in Zebrafish.
Shen ZX, Xia PP, Cai JL … +4 more , Gu HH, Zhang Y, Wu ZB, Sun YM
Biochem Genet · 2025 Nov · PMID 41236688 · Publisher ↗
Variants in several genes have been linked to congenital syndromes involving anophthalmia and microphthalmia; however, the specific genotypes and phenotypes associated with these conditions remain unclear. Calsequestrin...
Variants in several genes have been linked to congenital syndromes involving anophthalmia and microphthalmia; however, the specific genotypes and phenotypes associated with these conditions remain unclear. Calsequestrin 2 (CASQ2) is highly expressed in rodent extraocular muscles, but its role in eye development is unclear. In a previous study, we identified a novel CASQ2 (c.241G > A, p.A81T) mutation, which replaces the alanine residue at amino acid 81 with threonine, in a patient with catecholaminergic polymorphic ventricular tachycardia (CPVT). Here, we investigated its effect on eye development. The impact of the CASQ2 mutation on eye development was studied in zebrafish embryos by overexpressing the mutant gene. RNA sequencing was used to identify changes in gene expression, involving over 22,000 genes. Overexpression of the CASQ2 mutation in zebrafish embryos resulted in significant eye morphology changes, with 27.78% of embryos exhibiting anophthalmia or microphthalmia, compared to none in the control group (P < 0.0001). RNA sequencing revealed 1,240 differentially upregulated and 1158 downregulated genes in the CASQ2 mutant group. Nine genes significantly associated with eye development were identified, along with alterations in the Wnt signaling pathway and enrichment of six pathways: arginine and proline metabolism, apoptosis, lysosomes, biosynthesis of unsaturated fats, phototransduction, and p53 signaling. The novel CASQ2 mutation (c.241G > A, p.A81T) adversely affects eye development in zebrafish embryos, suggesting additional molecular pathways involved in anophthalmia and microphthalmia. This finding will enhance our understanding of the genetic basis of these eye conditions and may inform future research and therapeutic strategies.
Evaluation of Immune Gene Expression Reveals Immunomodulatory Activity of Chlorella vulgaris in a Mouse Model.
Robben DM, Amin Z, Budiman C … +1 more , Kumar VS
Biochem Genet · 2025 Nov · PMID 41236687 · Publisher ↗
Chlorella vulgaris, a unicellular freshwater microalga, is widely recognised as a functional food and supplement with immunomodulatory properties attributed to its bioactive components. These bioactive components include...
Chlorella vulgaris, a unicellular freshwater microalga, is widely recognised as a functional food and supplement with immunomodulatory properties attributed to its bioactive components. These bioactive components include proteins, fatty acids, polysaccharides, pigments, and antioxidants. Nonetheless, a comprehensive gene-expression profile related to the innate and adaptive immune responses of C. vulgaris supplementation is lacking. This study aimed to evaluate the immunomodulatory effects of C. vulgaris in a mouse model through the oral administration of C. vulgaris biomass into BALB/c mice. Seven days after the oral administration, spleen tissues were analysed via a qPCR array to assess the expression of 84 genes related to the innate and adaptive immune response. Results show a significant upregulation (fold change > 2.0) of seven essential immune genes, such as Irf7, Mpo, Stat1, Tlr6, Tlr7, Tlr9, and Tyk2. In contrast, five immune-related genes, including Ccl5, Ccr6, Csf2, Myd88, and Rorc, were significantly downregulated (fold change <-2.0). These results show a comprehensive immune-gene expression profile elicited following seven days after the oral administration of C. vulgaris in mice. This work offers novel insights into the immunomodulatory properties of C. vulgaris through the immune gene expression profile it exhibited and underscores its known potential as an alternative therapy to boost immunity in various health conditions.
LMNB2 Regulates Esophageal Carcinoma Stemness and Warburg Effect by Modulating the p38 MAPK Signaling Pathway.
Zhu X, Zhao X, Cui Y
Biochem Genet · 2025 Nov · PMID 41236686 · Publisher ↗
Esophageal carcinoma (ESCA) represents a highly aggressive malignancy with limited therapeutic options. Mounting evidence indicated that Nuclear Lamin B2 (LMNB2) was involved in tumor progression through modulation of mu...
Esophageal carcinoma (ESCA) represents a highly aggressive malignancy with limited therapeutic options. Mounting evidence indicated that Nuclear Lamin B2 (LMNB2) was involved in tumor progression through modulation of multiple signaling pathways. However, the investigation of LMNB2 role in tumor cell stemness and the Warburg effect remains inconclusive. This study utilized the UALCAN database to perform pan-cancer, clinical sample and cell line analyses. Western blot validation demonstrated substantial LMNB2 overexpression in ESCA cells. Silencing LMNB2 expression significantly repressed ESCA cells stemness and Warburg effect. Integrated bioinformatics analyses using Linkedomics, Funrich, and String databases identified the p38 MAPK pathway as a downstream mediator. In vitro experiments verified the regulatory impact of LMNB2 on the p38 phosphorylation in the MAPK signaling pathway, implicated in the regulation of tumor sphere formation and the Warburg effect. LMNB2 also exhibited a regulatory role in tumor growth within the mouse xenograft model. This study proposed that LMNB2 could emerge as a novel therapeutic strategy for treating ESCA.
Determination of the Frequency of HBB (c.20 A > T) Gene Mutation in the Nigerian and Zimbabwean Populations in Northern Cyprus.
Çobanoğulları H, Gbassay DM, Zaway MF … +1 more , Ergören MÇ
Biochem Genet · 2025 Nov · PMID 41236685 · Publisher ↗
Sickle cell disease (SCD) is one of the most frequently observed monogenic diseases and is a major health problem worldwide. It is particularly prevalent in some countries such as Africa, the Middle East and the Mediterr...
Sickle cell disease (SCD) is one of the most frequently observed monogenic diseases and is a major health problem worldwide. It is particularly prevalent in some countries such as Africa, the Middle East and the Mediterranean region. Due to a single point mutation in the β-globin gene HBB (c.20 A > T), the glutamic acid is replaced by valine amino acid at the sixth position of the β-globin chain (p.Glu6Val), which leads to changes in the properties of the hemoglobin protein and affects the conformation of red blood cells. Importantly, the distribution of the sickle hemoglobin (HbS) allele varies worldwide. Without knowing the distribution of this allele, the true significance of this gene mutation for SCD is unknown. The aim of this study is to determine the frequency of the HBB (c.20 A > T) gene mutation in the Nigerian and Zimbabwean populations in Northern Cyprus. Blood samples were collected from 208 volunteers (100 Nigerians and 108 Zimbabweans) living in Northern Cyprus. DNA was extracted from peripheral leukocytes. Genotyping was performed by real-time polymerase chain reaction (RT-PCR). The distribution of the allele and genotype frequencies of the HBB (c.20 A > T) gene mutation were tested for Hardy-Weinberg equilibrium. Notably, the distribution of the HBB (c.20 A > T) gene mutation in the Zimbabwean population was found to be in agreement with Hardy-Weinberg equilibrium (p > 0.05), suggesting a consistent allele frequency in this group. Particularly, the frequency of the HbS allele was determined to be 25% and 12.5% in the Nigerian and Zimbabwean populations, respectively. In summary, the results of this study have contributed to the literature by determining the frequency of the HBB (c.20 A > T) gene mutation in the Nigerian and Zimbabwean populations. This is crucial for understanding the true significance of this particular gene mutation for SCD in these two populations, which may also shed light on the development of better structured and preventive strategies.
PIP4K2A: A Novel CD8+ T Cell-Related Biomarker Associated with Lung Function Decline in COPD.
Huang S, Lin S, Ke J … +3 more , Lei S, He Z, Duan M
Biochem Genet · 2025 Nov · PMID 41217726 · Publisher ↗
CD8+ T cells play a pivotal role in Chronic obstructive pulmonary disease(COPD) inflammatory pathogenesis. To elucidate the molecular mechanisms underlying CD8+ T cell involvement in COPD development, this study employed...
CD8+ T cells play a pivotal role in Chronic obstructive pulmonary disease(COPD) inflammatory pathogenesis. To elucidate the molecular mechanisms underlying CD8+ T cell involvement in COPD development, this study employed an integrated approach combining bioinformatics analysis with experimental validation to identify CD8+ T cell-associated marker genes, construct a diagnostic model, and evaluate their correlation with pulmonary function in COPD. Lung tissue sequencing data from COPD patients and controls were obtained from the Gene Expression Omnibus(GEO) database. Differential expression analysis was conducted using R on both bulk RNA-seq and single-cell RNA-seq datasets. LASSO regression analysis was subsequently applied to identify hub genes, followed by functional annotation through Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses. Linear regression analysis assessed correlations between key genes and pulmonary function parameters, with qRT-PCR validation performed on three lung function-associated genes using clinical samples from COPD patients and healthy controls. Our analyses identified seven CD8+ T cell-related genes (CST7, HSPA8, PXN, YPEL5, PIP4K2A, CDKN1B, PIK3IP1) that collectively formed a highly effective diagnostic model. Among these, HSPA8, PIP4K2A, and YPEL5 demonstrated significant correlations with impaired lung function in COPD patients. qRT-PCR validation confirmed PIP4K2A expression patterns in clinical samples, consistent with microarray data. These findings establish CD8+ T cell-associated biomarkers for COPD, with PIP4K2A expression showing particular relevance to lung function decline, thereby providing new molecular insights into CD8+ T cell-mediated mechanisms in COPD pathogenesis.
Stable Transgenerational Epimutants in Okra Induced by Sodium Butyrate: A Novel Pathway to Functional Breeding.
Sasipriya S, Dushyantha Kumar BM, Adivappar N
Biochem Genet · 2025 Nov · PMID 41217725 · Publisher ↗
Histone deacetylation chemicals such as sodium butyrate can induce phenotypic epigenetic variations in okra varieties. Some of these induced variations can be transmitted across multiple generations with uniformity and s...
Histone deacetylation chemicals such as sodium butyrate can induce phenotypic epigenetic variations in okra varieties. Some of these induced variations can be transmitted across multiple generations with uniformity and stability over locations. Epigenetic modifications act as an extraneous source of variations in organisms possessing them. Epigenetic marks are observed in natural plant populations; however, the chemical induction, identification and heritable transmission of visible epigenetic variations remain relatively rare. In our study, we have tried inducing phenotypic variations in two open pollinated okra varieties, namely, Arka Anamika and Arka Abhay using a histone deacetylase inhibitor, sodium butyrate. A wide spectrum of visible mutations for various traits was observed among the treated plants. One particular mutant plant lacking purple color pigmentation on the backside of the petals was identified and observed to be reappearing in successive generations. The trait was stably inherited across generations and locations following a non-Mendelian pattern of inheritance. The study showed that mutations can be artificially induced epigenetically in plants and some of these induced mutations can be stably inherited by subsequent generations, exhibiting stable and uniform performance.
Evaluating the Effect of Exosome-Encapsulated miR-4289 on Menstrual Blood-Derived Mesenchymal Stem Cells from Endometriosis Patients.
Mahmoudi S, Sheikholeslami A, Roodbari NH … +1 more , Ehsani E
Biochem Genet · 2025 Nov · PMID 41217724 · Publisher ↗
Endometriosis is a benign yet chronic gynecological disorder characterized by dysregulation of processes such as inflammation, angiogenesis, migration, apoptosis, and proliferation. Menstrual blood-derived endometrial st...
Endometriosis is a benign yet chronic gynecological disorder characterized by dysregulation of processes such as inflammation, angiogenesis, migration, apoptosis, and proliferation. Menstrual blood-derived endometrial stem cells play a crucial role in the retrograde development and progression of endometriotic lesions. To evaluate the therapeutic potential of exosomes derived from menstrual blood-derived stem cells, exosomes from non-endometriotic MenSCs (NE-MenSCs), both unmodified (Exo) and transfected with miR-4289, were applied as treatments to MenSCs from the endometriosis cell line (E-MenSCs). Publicly available databases were used to identify key genes and signaling pathways implicated in endometriosis, from which miR-4289 was selected as an effective regulatory microRNA. Following treatment, cellular migration was assessed by scratch assays; gene expression was evaluated via real-time PCR; protein levels of ROS, IL-10, and IL-1β were measured by ELISA; and ESR1, CTNNB1, and Ki67 levels were determined by Western blotting. The results indicate that treatments significantly reduced the expression of genes associated with inflammation, proliferation, migration, and the Wnt/β-catenin pathway. Scratch assays and reductions in MMP9 expression suggest decreased migration in the Exo and miR-Exo groups. The expression of CTNNB1, IL-1β, and IL-10 was significantly downregulated in treated groups compared to E-MenSCs. In addition, KRAS and IDO1 expression levels were significantly decreased following treatment, and Ki67 protein levels were notably reduced in the miR and miR-Exo groups. These findings highlight the therapeutic potential of MenSC-derived exosomes loaded with miR-4289 as a promising and novel strategy for treating endometriosis.
Novel Frameshift Deletion Pathogenic Variant Characterization in Tuberous Sclerosis-2 Using Exome Sequencing and Molecular Dynamics Simulation.
Fadaie M, Biglari S, Vahidnezhad H … +7 more , Tabatabaiefar MA, Moghaddam AS, Khalafiyan A, Onagh L, Sarli A, Khorshid HRK, Esmaeilzadeh E
Biochem Genet · 2025 Nov · PMID 41217723 · Publisher ↗
Tuberous sclerosis complex (TSC) is a rare genetic disorder with an autosomal dominant inheritance pattern, affecting roughly 1 in 6,000 to 1 in 10,000 live births. The genetic mutations in the TSC1 or TSC2 genes lead to...
Tuberous sclerosis complex (TSC) is a rare genetic disorder with an autosomal dominant inheritance pattern, affecting roughly 1 in 6,000 to 1 in 10,000 live births. The genetic mutations in the TSC1 or TSC2 genes lead to this condition, while TSC2 mutations tend to produce more severe symptoms at an earlier age. The research uses exome sequencing (ES) and molecular dynamics (MD) simulations to detect and study a novel pathogenic TSC2 frameshift deletion variant and its structural and functional consequences. The causative variant was identified by ES and then confirmed by Sanger sequencing and cosegregation analysis. MD simulations with GROMACS software were used to investigate the structural and functional impacts of the variant on the tuberin protein. The American College of Medical Genetics and Genomics (ACMG) guidelines were followed for the variant interpretation. We identified a novel de novo frameshift deletion variant, c.3647_3651del (p.Leu1216Profs*16), in the TSC2 gene in a 12-year-old boy with skin lesions, seizures, and autistic behaviors. A frameshift deletion variant was detected in the 31st exon of TSC2. It fulfills the pathogenic criteria established by ACMG guidelines. The structural modeling and molecular dynamics simulations show that the mutation causes three main effects: it eliminates the GAP domain while breaking intramolecular hydrogen bonds. It decreases solvent exposure, which results in decreased stability and modified conformational movements of tuberin. This study highlights the effective use of ES for TSC diagnosis and genetic counseling. Our computational analysis provides predictive molecular insights into the potential mechanisms driving TSC pathology. The combined approach could aid in developing new therapeutic and management strategies for TSC. These findings suggest that such variants could be amenable to therapeutic modulation of the mTOR pathway, for example, through mTOR inhibitors.
The G→C rs590352 in the Protein-Coding Region of ATXN7L3B Gene Upregulates Its Expression In Vivo.
Degtyareva A, Antontseva E, Ershov N … +1 more , Merkulova T
Biochem Genet · 2025 Nov · PMID 41217722 · Publisher ↗
Previously using the omics data on allele-asymmetric gene expression (RNA-seq) and allele-asymmetry in the binding of regulatory proteins (ChIP-seq), we have determined rs590352 G→C as a potential regulatory polymorphism...
Previously using the omics data on allele-asymmetric gene expression (RNA-seq) and allele-asymmetry in the binding of regulatory proteins (ChIP-seq), we have determined rs590352 G→C as a potential regulatory polymorphism. Substitution G→C is situated in the protein-coding region of gene ATXN7L3B and is synonymic. The product of this gene competes with protein ATXN7L3 of the DUB module of transcription coactivator SAGA complex. The goal of our work is to study the effect of single nucleotide substitution G→C on the activity of putative cis-regulatory element in the exon 1 of ATXN7L3B. We use electrophoretic mobility shift assay (EMSA) to demonstrate that the G→C (rs590352) substitution damages the binding sites of certain transcription factors in the region of its localization. Dual luciferase assay demonstrates that this substitution significantly decreases the reporter gene expression when inserting the cassettes of double or triple repeats of the corresponding element upstream of heterologous promoter. The allele-asymmetric in vivo ATXN7L3B expression is lower in the case of allele C as compared with that of allele G. These data are useful for both the understanding of the regulation of poorly studied gene ATXN7L3B and a deeper insight into the functional role of SNPs in gene coding regions.
Identification of Peroxisome Proliferator-Activated Receptors as Novel Regulators of Bovine Hepcidin Expression.
Matsumura M, Yasuda A, Murakami M … +1 more , Funaba M
Biochem Genet · 2025 Nov · PMID 41214318 · Publisher ↗
Hepcidin centrally regulates systemic iron status. We previously revealed that activities of trans-factor to induce hepcidin expression are distinct between cattle and humans/mice in which regulation of hepcidin expressi...
Hepcidin centrally regulates systemic iron status. We previously revealed that activities of trans-factor to induce hepcidin expression are distinct between cattle and humans/mice in which regulation of hepcidin expression is well-examined. Here we characterized the cis-element of the bovine hepcidin promoter. Bovine hepcidin transcription was stimulated by co-expression of peroxisome proliferator-activated receptor (PPAR) and retinoid X receptor (RXR) by a stimulus screening for regulator of transcription. PPARα and PPARγ, lipid metabolism-related transcription factors, cooperatively increased expression of bovine hepcidin reporter with RXR in a synthetic agonist-independent manner. PPARα is predominantly expressed in the liver, and down-regulation of PPARα expression decreased hepcidin mRNA levels in bovine hepatocytes. The PPAR-response element (PPRE) that is responsible for PPAR-mediated reporter activation was identified in the region spanning between nt -192 to nt -173 on bovine hepcidin promoter. In contrast, the putative PPRE was detected in ruminant hepcidin promoter but not in the compatible regions of hepcidin promoter from humans, mice, rats, pigs, dogs, and cats. Consistent with the results, co-expression of PPAR and RXR did not increase the expression of hepcidin reporter prepared from these animal species. The present study reveals a novel ruminant-specific stimulation of hepcidin transcription, which suggests the regulation of hepcidin-involved iron metabolism related to hepatic lipid metabolism.
Identification of the Dynamic Expression Patterns of Immune Genes in the Peripheral Blood of Acute Ischemic Stroke Patients.
Jin J, Li L, Li D … +9 more , Wang X, He N, Tian L, Chen B, Li X, Zhang L, Chen Z, Qiao L, Wang J
Biochem Genet · 2025 Nov · PMID 41214317 · Publisher ↗
Stroke is the second primary cause of death in the world and a main cause of disability, with ischemic stroke accounting for 80% of stroke cases. Under normal physiological conditions, there is a relative balance between...
Stroke is the second primary cause of death in the world and a main cause of disability, with ischemic stroke accounting for 80% of stroke cases. Under normal physiological conditions, there is a relative balance between the proinflammatory response and the anti-inflammatory response in brain tissue. Once ischemic stroke occurs, the balance is disrupted, and subsequent immune dysfunction occurs. However, the dynamic gene expression patterns underlying the immune-related mechanisms of acute ischemic stroke (AIS) are still not fully understood. In this study, through protein‒protein interaction network construction, random forest algorithm and immune cell subtype distribution evaluation, the 7 hub immune genes, namely, C5AR1, CD79B, TLR4, FLT3LG, IGF2R, NCR3 and PAK2, were identified. The peripheral blood of 60 AIS patients and 20 healthy controls was collected and grouped according to onset time and blood collection time. qRT‒PCR was used to measure the expression levels of hub immune genes in the peripheral blood mononuclear cells (PBMCs) of the AIS groups and control group. The results indicated that the hub immune genes were associated the onset and development of AIS. According to Pearson correlation analysis, the hub immune genes may be correlated with the dynamic immune response after AIS to some extent. In summary, our study identified 7 hub immune genes and verified the correlations between the 7 hub immune genes and the dynamic immune response after AIS. Furthermore, these genes may be novel candidate biomarkers or therapeutic targets in AIS.
Thyroid Peroxidase and its Gene Variants as Diagnostic Markers in Subclinical Hypothyroidism: Evidence from a Duhok Case-Control Study.
Adam LN, Abbas AM
Biochem Genet · 2025 Nov · PMID 41214316 · Publisher ↗
Elevated TSH with normal T3 and T4 levels is a sign of subclinical hypothyroidism (SCH), is often linked to autoimmune thyroiditis. Thyroid peroxidase antibodies (anti-TPO) are early markers, but their diagnostic value a...
Elevated TSH with normal T3 and T4 levels is a sign of subclinical hypothyroidism (SCH), is often linked to autoimmune thyroiditis. Thyroid peroxidase antibodies (anti-TPO) are early markers, but their diagnostic value and genetic associations in Middle Eastern populations are not well understood. This study assessed serum TPO levels and TPO gene polymorphisms in relation to SCH in Duhok, Iraq (September-December 2024). In a case-control design, 78 patients with SCH and 75 age- and gender-matched euthyroid controls were recruited. Serum levels of TSH, T3, T4, Vitamin D, and anti-TPO were measured. Genotyping of the TPO T1936C variant was performed by ARMS-PCR. Two-sided statistical tests were applied. Correlations were assessed using Spearman's ρ, and genotype frequencies were tested for Hardy-Weinberg equilibrium. Diagnostic performance of anti-TPO was evaluated by receiver operating characteristic (ROC) analysis, including area under the curve (AUC), 95% CI, and Youden index. Patients with SCH showed significantly elevated anti-TPO levels compared to controls (107.5 ± 149.6 vs. 39.5 ± 81.6 IU/mL; p = 0.014). ROC analysis identified ≥ 60.4 IU/mL as the optimal anti-TPO cut-off for SCH prediction (AUC = 0.62, 95% CI: 0.52-0.71, sensitivity = 47.44%, specificity = 89.33%). TPO levels correlated positively with TSH (Spearman ρ = 0.174, p = 0.031), but not with T3, T4, or Vitamin D. TPO (T1936C) gene polymorphism analysis revealed no significant association with SCH (AA genotype: 80.77% in cases vs. 77.33% in controls), (GA genotype: 19.23% in cases vs. 22.67% in controls) p = 0.85. The GG genotype was absent in both groups. Anti-TPO antibodies demonstrated high specificity but modest sensitivity as diagnostic markers for SCH. The TPO T1936C variant was not associated with SCH, though this null finding may reflect the study's limited statistical power. These results highlight the role of autoimmune markers in SCH diagnosis within the Kurdish population of Duhok, Iraq.
Retraction Note: TFAP2C Activates CST1 Transcription to Facilitate Breast Cancer Progression and Suppress Ferroptosis.
Yuan L, Zhou D, Li W … +3 more , Guan J, Li J, Xu B
Biochem Genet · 2026 Feb · PMID 41207954 · Publisher ↗
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ADAMTS6 Promotes Angiogenesis and Tumor Growth in Gastric Carcinoma.
Luo K, Hu B
Biochem Genet · 2025 Oct · PMID 41144105 · Publisher ↗
A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) protease family involves a critical member ADAMTS6, which is implicated in the pathogenesis of various cancers. This study explores the function of...
A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) protease family involves a critical member ADAMTS6, which is implicated in the pathogenesis of various cancers. This study explores the function of ADAMTS6 in tumor growth and angiogenesis in gastric carcinoma (GC). Using the TCGA-STAD dataset, key genes closely associated with GC prognosis were screened, and their correlation with the angiogenesis pathway was evaluated. In vitro, a GC cell model with ADAMTS6 knockdown was established, and cell proliferation, migration, invasion, and apoptosis were systematically assessed. The regulatory effect of ADAMTS6 on the angiogenic capacity of human umbilical vein endothelial cells (HUVECs) was determined via tube formation assay. In vivo, a GC xenograft mouse model was established to monitor tumor growth, and the effects of ADAMTS6 knockdown on tumor proliferation, apoptosis, and angiogenesis were comprehensively evaluated using immunohistochemistry, TUNEL staining, immunofluorescence, and Western blot analysis. ADAMTS6 was highly expressed in GC tissues and cell lines, and its expression was positively correlated with poor prognosis and tumor angiogenesis. Silencing ADAMTS6 significantly inhibited GC cell proliferation, migration, and invasion, while inducing apoptosis and attenuating the pro-angiogenic effect on HUVECs in vitro. Consistently, in vivo experiments confirmed that ADAMTS6 knockdown markedly suppressed tumor growth, as evidenced by reduced tumor volume and weight. Moreover, the expression of angiogenesis-related markers was downregulated following ADAMTS6 silencing. ADAMTS6 facilitates tumor growth and angiogenesis in GC and might act as a valuable biomarker for prognosis and a candidate target for anti-angiogenic therapeutic approaches.
TRIM Protein Superfamily in Breast Cancer: Yin and Yang.
Nenasheva V, Tarantul V
Biochem Genet · 2025 Oct · PMID 41114878 · Publisher ↗
Breast cancer (BC) remains the most prevalent malignancy among women and a leading cause of cancer-related mortality worldwide. Despite significant advances in recent decades, the molecular mechanisms underlying BC patho...
Breast cancer (BC) remains the most prevalent malignancy among women and a leading cause of cancer-related mortality worldwide. Despite significant advances in recent decades, the molecular mechanisms underlying BC pathogenesis are not yet fully elucidated. Emerging evidence indicates that more than half of the members of the tripartite motif (TRIM) protein superfamily, the majority of which exhibit E3 ubiquitin ligase activity, contribute to BC initiation, progression, and metastasis by exerting functions as either oncoproteins or tumor suppressors. TRIM proteins participate in diverse cellular processes and signaling pathways. In this review, we discuss the specific molecular mechanisms by which TRIM proteins influence BC development, including post-transcriptional modifications, regulation of apoptosis and autophagy, cell cycle control, and metabolic reprogramming of glucose and lipid pathways. A notable feature of TRIM proteins is their engagement in diverse cellular processes and signaling pathways, coupled with their ability to play opposing roles - either promoting or inhibiting BC development - thus reflecting a 'yin and yang' paradigm. Collectively, current data suggest that TRIM genes and their protein products represent promising targets for therapeutic intervention and potential biomarkers for BC prognosis and disease progression.
A Deleterious Variant in MBOAT7 Causes Intellectual Disability in an Iranian Family: An Example of Reassignment of Variants of Uncertain Significance.
Saba N, Naghinejad M, Khaniani MS … +3 more , Sadeghvand S, Derakhshan SM, Taheri M
Biochem Genet · 2025 Oct · PMID 41099992 · Publisher ↗
Membrane-bound O-acyltransferase domain-containing member 7 (MBOAT7) plays an irreplaceable role in lipogenesis and neural development. Over the past decade, a few variants in MBOAT7 have been associated with intellectua...
Membrane-bound O-acyltransferase domain-containing member 7 (MBOAT7) plays an irreplaceable role in lipogenesis and neural development. Over the past decade, a few variants in MBOAT7 have been associated with intellectual disability (ID), and a spectrum of clinical symptoms, including seizures, autism spectrum disorders (ASD), and speech impairment. DNA samples from two of the three affected members of a large Iranian Azeri family with moderate ID and no major dysmorphic features were investigated by whole exome sequencing (WES). Bioinformatic tools were used to identify and evaluate the pathogenicity of the candidate variants. The most likely causative variant was pursued by Sanger sequencing in patients and their relatives. ACMG guidelines and in silico analysis, including molecular modeling, were used to validate the identified variant of uncertain significance (VUS). An in-frame deletion, NM_024298.5: c.37_39 del (p.Leu13del) in the MBOAT7 gene, which had not been previously reported with homozygous genotype, was identified as a possible cause of the clinical conditions in patients. Sanger analysis confirmed the recessive inheritance pattern of this variant in probands and 14 relatives. In-silico modeling of the mutant protein revealed structural changes resulting from removing a highly conserved amino acid. The current study has expanded the MBOAT7 gene variant spectrum and clarified variable phenotypic features to the associated ID criteria. Meanwhile, we have provided insights into the importance of the MBOAT7 protein's first alpha helix in terms of its functionality and solid evidence regarding a VUS's pathogenicity. Additionally, this study presents the oldest recorded case of MBOAT7-related ID in a 51-year-old female to date.
German Chamomile (Matricaria chamomilla) Induces Cytochrome P450 Expression Through Increased BMAL1 Protein Expression in Liver Nuclei.
Ikeda M, Tsurudome Y, Enrin M … +3 more , Wada Y, Horiguchi M, Ushijima K
Biochem Genet · 2025 Oct · PMID 41091411 · Publisher ↗
German chamomile (Matricaria chamomilla) is a medicinal herb that promotes improved digestion and reduces insomnia. Although it is widely used worldwide, the mechanism of induction of drug-metabolizing enzymes is unknown...
German chamomile (Matricaria chamomilla) is a medicinal herb that promotes improved digestion and reduces insomnia. Although it is widely used worldwide, the mechanism of induction of drug-metabolizing enzymes is unknown. We found that German chamomile extracts induced cytochrome P450 expression at the transcriptional stage. Cyp3a11 expression is decreased at night in wild-type mice, but German chamomile extract induced nocturnal Cyp3a11 and Cyp1a2 expression. German chamomile extract increased the nuclear protein expression of the clock gene BMAL1, which drives and abolishes the rhythm of Cyp3a11 expression. By contrast, German chamomile extract did not significantly alter clock gene expression in the suprachiasmatic nucleus (SCN). Similarly, it did not affect the mRNA expression of the clock genes in the kidneys. Because it did not induce the mRNA expression of ATP-binding cassette (ABC) transporters (Abcb1a, Abcc2, Abcc4, and Abcg2) in the kidney, German chamomile extract had no effect on the transcription of pharmacokinetics-related molecules other than CYPs. German chamomile extract promoted liver-selective nuclear transfer rhythm changes in clock genes and induced the expression of CYPs. This study may help to explain the mechanism of drug interactions associated with chronic German chamomile extract consumption.
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