Biochemical Genetics[JOURNAL]
Sun
200 papers
CD27 Neutralization Attenuates Rheumatoid Arthritis by Suppressing.
Lu A, Pu L, Tian Y … +3 more , Song J, Luo D, Wu J
Biochem Genet · 2026 Apr · PMID 42033547 · Publisher ↗
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and destruction. Identifying novel therapeutic targets is crucial for improving RA treatment. This study aimed to identify imm...
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and destruction. Identifying novel therapeutic targets is crucial for improving RA treatment. This study aimed to identify immune-related biomarkers in RA and investigate the potential of CD27 as a therapeutic target. We employed bioinformatics analysis of gene expression data from RA patients and healthy controls (GSE55457), followed by machine learning approaches (LASSO regression and Boruta algorithm) to identify potential biomarkers. Findings were validated in an independent dataset (GSE55235). The therapeutic potential of CD27 neutralization was evaluated in a collagen-induced arthritis (CIA) mouse model. Mechanisms were explored through quantitative real-time PCR, Western blot analysis, ELISA, and flow cytometry to assess T cell subsets, cytokine profiles, and signaling pathways. Bioinformatics analysis identified 714 differentially expressed genes, and machine learning analyses identified CD27, CD24, TNFRSF4, and PDCD1LG2 as potential RA biomarkers, all demonstrating strong diagnostic performance. CD27 showed significant positive correlations with T lymphocyte infiltration. In the CIA model, CD27 neutralization significantly reduced arthritis severity scores. This therapeutic effect was associated with suppression of Th1 responses, evidenced by significantly decreased serum levels of Th1 cytokines (IFN-γ, IL-2, TNF-α) and reduced CD4 + IFN-γ + cell populations, while Th2-related cytokines (IL-4, IL-5) remained largely unaffected. Mechanistically, CD27 neutralization attenuated phosphorylation of AKT and NF-κB p65 in vivo, while p38 MAPK remained unchanged. In vitro, recombinant CD27 protein stimulation of naive CD4 + T cells promoted Th1-biased differentiation, increasing CD4 + IFN-γ + cells and enhancing the phosphorylation of NF-κB p65 and AKT. Our study identifies CD27 as a potential therapeutic target in RA. CD27 neutralization attenuates arthritis severity by suppressing Th1 responses, possibly through modulation of AKT and NF-κB signaling pathways. These findings provide new insights into RA pathogenesis and suggest CD27 as a promising target for RA treatment.
Network Pharmacology and Molecular Docking Reveal Myricanone's Role in Alleviating Ischemic Cerebral Infarction via Targeting MAPK14.
Zhao B, Zhang J
Biochem Genet · 2026 Apr · PMID 42029879 · Publisher ↗
Myricanone (MYR) is the active component of Chuanxiong Rhizoma, which has the potential to reduce blood lipids and anti-atherosclerosis. To explore the potential mechanism of MYR in the treatment of ischemic cerebral inf...
Myricanone (MYR) is the active component of Chuanxiong Rhizoma, which has the potential to reduce blood lipids and anti-atherosclerosis. To explore the potential mechanism of MYR in the treatment of ischemic cerebral infarction (ICI) injury. This study employed network pharmacology to screen the active components of Chuanxiong Rhizoma and identify its potential targets. Through protein-protein interaction (PPI) network analysis, MAPK14 was identified as a core hub gene. Subsequently, molecular docking validated the binding affinity between MYR and MAPK14. To assess MAPK14’s clinical relevance, RT-qPCR measured its expression levels in peripheral blood mononuclear cells (PBMCs) from ICI patients, correlating it with disease severity (NIHSS score) and prognostic indicators (mRS score). Furthermore, the neuroprotective effects of MYR and its regulatory mechanism on MAPK14 were validated through an oxygen-glucose deprivation (OGD) in vitro model using HMC3 microglia and behavioral tests (rotarod test and Morris water maze) in a mouse ICI model. Five effective components of Chuanxiong Rhizoma were identified. They targeted 44 genes, of which MAPK14 was the core target. Molecular docking experiments showed that MYR had a strong binding affinity with MAPK14. In addition, MAPK14 expression in the PBMCs of ICI patients was positively correlated with disease severity and poor prognosis. In vitro and in vivo experiments confirmed that MYR significantly alleviated OGD-induced human microglia damage and improved ICI mice’s motor, learning, and memory deficits by down-regulating the expression of MAPK14. MYR may effectively inhibit ICI development by down-regulating MAPK14, providing a scientific basis for clinical application in ICI.
Identification of Autophagy-related Genes of the Osteoarthritis Using Machine Learning Algorithm.
Zhang Z, Wang H, Cheng X … +4 more , Zhang Z, Hou Z, Liu Z, Gao Y
Biochem Genet · 2026 Apr · PMID 42012756 · Publisher ↗
Autophagy plays a significant role in the pathogenesis of osteoarthritis (OA). The objective of this study was to identify diagnostic signature genes associated with OA from the autophagy-related genes (ARGs). This study...
Autophagy plays a significant role in the pathogenesis of osteoarthritis (OA). The objective of this study was to identify diagnostic signature genes associated with OA from the autophagy-related genes (ARGs). This study first obtained gene expression profiles (GSE114007 and GSE57218) of OA cartilage from the GEO database and subsequently identified differentially expressed genes (DEGs) using the limma method. To further explore the biological functions of these DEGs in OA, Gene Ontology (GO) and KEGG enrichment analyses were conducted. Additionally, to screen for autophagy-related differentially expressed genes (ADEGs), the study visualized these genes using Venn diagrams. Next, the LASSO algorithm was applied to identify potential OA marker genes within the ADEGs. Finally, to validate the expression and effects of these genes, RT-qPCR analysis was performed in an in vitro OA model, and Western blotting was used to analyze the effects of gene overexpression in OA cells. The results demonstrated that PIM2, PTPN22, and RRAGD were identified as signature genes, exhibiting low expression levels with high diagnostic efficacy in OA samples from both experimental and test group datasets. Overexpression of PIM2, PTPN22, and RRAGD in OA cells showed suppression of inflammation-associated proteins (MMP13 and ADAMTS) and enhancement of cartilage matrix-associated proteins (Aggrecan and Collagen II). In conclusion, this study highlights PIM2, PTPN22, and RRAGD as novel and crucial diagnostic markers for OA through the utilisation of machine learning techniques, and may also offer novel insights for potential targeted therapeutic interventions in the future.
Cancer-Associated Fibroblasts-Derived Exosomal HOXC8 Promotes Glycolysis and Malignant Metastasis of Lung Cancer Cells via CDKN3.
Wu F, Qiao M
Biochem Genet · 2026 Apr · PMID 41999541 · Publisher ↗
Lung cancer, as one of the main causes of cancer-related deaths worldwide, has a high mortality rate and a poor prognosis. Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment, wh...
Lung cancer, as one of the main causes of cancer-related deaths worldwide, has a high mortality rate and a poor prognosis. Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment, which can regulate the behavior of cancer cells by secreting exosomes to transfer bioactive molecules. Homeobox C8 (HOXC8) is a homeobox gene that has been proven to be abnormally expressed in lung cancer, but the specific regulatory mechanism of it remains unclear. Firstly, CAFs, normal fibroblasts (NFs) and the exosomes secreted by them were separated and identified. The uptake of DIL-labeled exosomes by lung cancer cells was observed under a fluorescence microscope. Subsequently, the effects of CAFs-Exo and CAFs-Exo (si-HOXC8) on the viability, proliferation, apoptosis, migration, invasion, angiogenesis, and glycolysis of lung cancer cells were examined. Through bioinformatics analysis, Western blotting and qRT-PCR, the regulation of HOXC8 on Cyclin dependent kinase inhibitor 3 (CDKN3) in lung cancer cells was verified. A rescue experiment was carried out to investigate the effect of the HOXC8/CDKN3 axis on lung cancer cells. The CAFs-Exo was successfully extracted, which could be taken up by lung cancer cells. The upregulation of HOXC8 expression was found in CAFs-Exo. CAFs-derived exosomal HOXC8 deficiency hindered lung cancer cell viability, proliferation, migration, invasion, angiogenesis (endothelial cells), glycolysis, while facilitated apoptosis. HOXC8 could upregulate the expression of CDKN3. Besides, it was found that overexpression of CDKN3 can eliminate the inhibitory effect of knockdown of HOXC8 on lung cancer cells. The expression of HOXC8 in CAFs-Exo was upregulated, which could accelerate the growth, metastasis, glycolysis of lung cancer cells, and the angiogenic capacity of endothelial cells by facilitating the expression of CDKN3.
A Method for Imputing scRNA-seq Data Based on Mobile Graph Convolutional Generative Adversarial Networks.
Zhang Q, Hu M, Zhong Z … +4 more , Liu J, Li W, Xu J, Sun Z
Biochem Genet · 2026 Apr · PMID 41998476 · Publisher ↗
Single-cell RNA sequencing (scRNA-seq) data typically contains substantial missing values, which often leads to the loss of critical gene signal information and severely limits downstream analyses. Deep learning-based im...
Single-cell RNA sequencing (scRNA-seq) data typically contains substantial missing values, which often leads to the loss of critical gene signal information and severely limits downstream analyses. Deep learning-based imputation methods generally outperform shallow approaches in handling scRNA-seq data; however, most methods fail to consider the intrinsic relationships among genes, where gene expression is frequently regulated by other genes. Furthermore, existing methods remain inadequate in capturing complex intercellular spatial relationships and long-range dependencies. Therefore, we propose MGCGImpute, a deep learning model for scRNA-seq data imputation that integrates the multi-scale relational modeling capabilities of mobile graph convolutional networks with the distributional learning advantages of generative adversarial networks, achieving precise data reconstruction through learning enhanced spatial relational patterns and global data distribution characteristics. Experimental validation on multiple representative real-world scRNA-seq datasets using multidimensional evaluation metrics and 5-fold cross-validation demonstrates that MGCGImpute achieves superior performance in both imputation accuracy and biological plausibility.
WTAP-Driven m6A Modification of TIMP1 mRNA Promotes Sepsis-Induced Cardiomyocytes Injury.
Tang Y, Yi Z, Huang B … +3 more , Wu J, Tian B, Long G
Biochem Genet · 2026 Apr · PMID 41973152 · Publisher ↗
Sepsis-induced myocardial injury, characterized by severe myocardial dysfunction, is one of the most common and lethal complications of sepsis in clinical settings. However, the underlying pathogenesis is not fully under...
Sepsis-induced myocardial injury, characterized by severe myocardial dysfunction, is one of the most common and lethal complications of sepsis in clinical settings. However, the underlying pathogenesis is not fully understood. In this study, we conducted a combined analysis of mRNA-seq and MeRIP-seq datasets obtained from GEO, identifying 110 differentially expressed genes at both the transcriptional and m6A modification levels. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that these genes were primarily enriched in inflammation and immune response-related signaling pathways. Additionally, we identified 20 key genes involved in regulating myocardial injury during sepsis using Protein-Protein Interaction (PPI) analysis combined with the K-means clustering algorithm and MCC algorithm. Subsequently, the expression patterns of these 20 hub genes and their relationship with cardiac function were verified using transcriptome datasets from different species. The results showed that TIMP1 was the only gene significantly up-regulated in myocardial injury across different species and was closely associated with reduced cardiac function. Furthermore, through bioinformatics analysis, MeRIP sequencing, and dual luciferase reporter assays, we demonstrated that the abnormal up-regulation of TIMP1 in septicemia-induced myocardial injury is mediated by WTAP-driven m6A modifications, which enhance the stability of TIMP1 mRNA. Finally, we used lipopolysaccharide (LPS)-induced human cardiomyocytes AC16 to simulate a sepsis-induced myocardial injury model and conducted gene loss-function or rescue experiments. The results showed that targeted inhibition of the WTAP-m6A-TIMP1 axis can significantly improve LPS-induced myocardial cell damage. Collectively, these findings highlight the role of WTAP-mediated m6A modification in driving TIMP1 expression in sepsis-induced cardiomyocyte injury, potentially providing a new therapeutic target for sepsis-induced myocardial injury.
lncRNA DLGAP1-AS2 Modulates the TGF-β/Smad Signaling Pathway to Regulate Epithelial-Mesenchymal Transition in Renal Cell Carcinoma.
Cao H, Zhu J, Zhang L … +3 more , Li L, Ma L, Xie C
Biochem Genet · 2026 Apr · PMID 41964741 · Publisher ↗
Renal cell carcinoma (RCC) is a prevalent malignancy of the urinary system, but the role of lncRNA DLGAP1-AS2 in epithelial–mesenchymal transition (EMT) in RCC remains unclear. In this study, shRNA was transfected into R...
Renal cell carcinoma (RCC) is a prevalent malignancy of the urinary system, but the role of lncRNA DLGAP1-AS2 in epithelial–mesenchymal transition (EMT) in RCC remains unclear. In this study, shRNA was transfected into RCC cells to reduce lncRNA DLGAP1-AS2 expression. The effects of lncRNA DLGAP1-AS2 knockdown on RCC cell proliferation, cell cycle, invasion, and migration were evaluated using CCK-8, flow cytometry, Transwell, and scratch assays, respectively. Western blotting was used to measure the protein expression of E-cadherin, EGFR, Vimentin, and α-SMA, while immunofluorescence was performed to visualize E-cadherin expression. An RNA pull-down assay confirmed the interaction between lncRNA DLGAP1-AS2 and transforming growth factor-beta (TGF-β), and nucleocytoplasmic fractionation together with qRT-PCR was used to analyze its subcellular localization. RCC cells were transfected with lncRNA DLGAP1-AS2 shRNA, treated with a TGF-β inhibitor, or both, and qRT-PCR and Western blotting were subsequently used to quantify the expression of Snail, Slug, E-cadherin, EGFR, Vimentin, α-SMA, TGF-β, TGF-βRI, and p-Smad3. Knockdown of lncRNA DLGAP1-AS2 decreased proliferation, migration, and invasion and was accompanied by a shortened G0/G1 phase. Compared with the NC-shRNA group, the lncRNA DLGAP1-AS2 shRNA group showed significantly lower levels of EGFR, Vimentin, and α-SMA, along with higher E-cadherin expression. TGF-β was identified as a target of lncRNA DLGAP1-AS2, and lncRNA DLGAP1-AS2 was found to be localized in the cytoplasm. Treatment with a TGF-β inhibitor enhanced the effects of lncRNA DLGAP1-AS2 knockdown on EMT in RCC cells. Moreover, transfection with lncRNA DLGAP1-AS2 shRNA inhibited the TGF-β/Smad signaling pathway. These findings suggest that reduced expression of lncRNA DLGAP1-AS2 may contribute to RCC suppression by modulating the TGF-β/Smad signaling pathway to inhibit EMT.
Exploring the Role of DNA Methylation in the Epigenetic Landscape of Cancer.
Mustafa SK, Omar SZ, Gheni AI
Biochem Genet · 2026 Apr · PMID 41964740 · Publisher ↗
DNA methylation constitutes a key epigenetic modification that is essential for the regulation of gene expression, the maintenance of genomic integrity, and the establishment of cellular identity and lineage. Aberrations...
DNA methylation constitutes a key epigenetic modification that is essential for the regulation of gene expression, the maintenance of genomic integrity, and the establishment of cellular identity and lineage. Aberrations in the regulatory mechanisms controlling DNA methylation have been implicated in the pathogenesis of numerous diseases, most notably cancer. In malignant cells, DNA methylation landscapes are characteristically altered, exhibiting widespread hypomethylation across the genome coupled with site-specific hypermethylation, particularly within CpG islands located in gene regulatory regions. Early investigations identified Tumor Suppressor Genes (TSGs) as primary targets of such hypermethylation, thereby supporting a prevailing model in which epigenetic silencing of TSGs contributes to oncogenesis. However, recent advances in large-scale genomic and epigenomic profiling have revealed a more complex landscape, suggesting that the classical model may be insufficient to fully explain the role of DNA methylation in cancer development. This review aims to elucidate the molecular mechanisms underpinning aberrant DNA methylation in cancer and to critically evaluate its potential as a target for therapeutic intervention.
Salidroside Regulates DN Podocyte Injury Through the LncRNA ZEB1-AS1/miR-21-5p/PDCD4 Axis.
Li W, Gui L
Biochem Genet · 2026 Apr · PMID 41964739 · Publisher ↗
Salidroside (SAL) is a drug supplement with cytoprotective properties that can relieve the effects of diabetes-related complications. This study aims to investigate the function of SAL in diabetic nephropathy (DN). The e...
Salidroside (SAL) is a drug supplement with cytoprotective properties that can relieve the effects of diabetes-related complications. This study aims to investigate the function of SAL in diabetic nephropathy (DN). The expression of related genes and proteins was detected by RT-qPCR, western blot, immunofluorescence and immunohistochemistry. Cell proliferation and apoptosis were detected by CCK-8 and TUNEL. HE, Masson and PAS staining were used to evaluate the pathological changes of kidney in DN rats. The results showed that SAL suppressed miR-21-5p expression by upregulating lncRNA ZEB1-AS1(ZEB1-AS1) and thus promoting PDCD4 expression, inhibiting cell apoptosis, promoting podocyte proliferation and migration, and alleviating podocyte injury in DN. Further in vivo experiments demonstrated that SAL-treated rats exhibited decreases in blood urine nitrogen (BUN) and the urine albumin–creatinine ratio (ACR), and SAL ameliorated the severity of DN, while knocking down ZEB1-AS1 weakened the effect of SAL. Our data suggested that the upregulation of ZEB1-AS1 by SAL participated in the ceRNA network and had a key function in alleviating DN podocyte injury through ZEB1-AS1-miR-21-5p-PDCD4 crosstalk. In conclusion, this study demonstrated that SAL inhibited DN podocyte injury through the ZEB1-AS1/miR-21-5p/PDCD4 axis.
Next-Generation Therapies for Genetic Diseases: The Synergy of CRISPR and Gene Therapy.
Karwa P, Kharul A, Parekar V … +4 more , Labhade S, Sakle N, Bhole R, Kapare H
Biochem Genet · 2026 Apr · PMID 41964738 · Publisher ↗
The introduction of the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology has changed the game of gene therapy and promises surgical precision and efficacy in the process of addressing genetic...
The introduction of the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology has changed the game of gene therapy and promises surgical precision and efficacy in the process of addressing genetic disorders in humans. Gene therapy that commonly assumes insertion of functional DNA with the help of viral vectors has developed or rather undergone adaptation with the introduction of CRISPR-Cas mechanisms that make it possible to edit the genome, correct or regulate it and silence. It is a critical study that reviews mechanistic disparities among traditional and CRISPR bases types of gene therapy, based on benefits, shortcomings, and states of improvement till date, as far as clinical development is concerned. It talks about their historical evolution, molecular principles, delivery modes, and therapeutic promise of the CRISPR systems such as Cas9, Cas12, Cas13, base editing, and prime editing. It is of significant value to mention the application of CRISPR as a treatment in monogenic illnesses such as 2-thalassemia and Duchenne muscular dystrophy as well as the future use of CRISPR in complex and multifactorial diseases. Also, safety concerns, ethical issues, and delivery translational problems are discussed by the review and they are paramount to successful clinical translation of CRISPR-based therapeutics. The discussion highlights the revolutionary possibility of CRISPR in precision medicine and predetermines its expansion in the future healthcare genomic practice.
Whole-Genome Deep Learning Predicts Chemotherapy Response in Colorectal Cancer.
Sadeghi H, Seif F
Biochem Genet · 2026 Apr · PMID 41964737 · Publisher ↗
Chemotherapy response in colorectal cancer (CRC) exhibits significant heterogeneity, with current clinical predictors failing to capture complex genomic determinants of resistance. We developed a hybrid deep learning fra...
Chemotherapy response in colorectal cancer (CRC) exhibits significant heterogeneity, with current clinical predictors failing to capture complex genomic determinants of resistance. We developed a hybrid deep learning framework integrating convolutional neural networks (CNNs) and bidirectional long short-term memory (BiLSTM) networks to analyze whole-genome somatic mutations, evolutionary conservation, chromatin accessibility, and 3D genome architecture in 2,546 TCGA patients. An attention mechanism identified predictive genomic regions. The model achieved an AUC of 0.92 (95% CI: 0.89-0.94) in cross-validation and 0.88 (95% CI: 0.85-0.91) in independent validation, outperforming clinical models (ΔAUC = +0.18, p < 0.001). Key predictors included non-coding variants in TP53, KRAS, and PIK3CA regulatory regions. Triple-positive patients (mutations in all 3 regions) had significantly worse progression-free survival (HR = 4.7, p < 0.001). Our framework enables accurate chemotherapy response prediction and reveals novel non-coding resistance mechanisms, advancing precision oncology in CRC.
Assessment of Genetic Diversity and Population Structure on Azadirachta indica A. Juss. in an Urban Metropolitan: Ahmedabad, India.
Kavithiya JJ, Prajapati KV, Trivedi PG … +1 more , Sindhav GM
Biochem Genet · 2026 Apr · PMID 41945285 · Publisher ↗
Azadirachta indica (A. indica) A. Juss., commonly known as Neem, is a valuable multipurpose tree with profound medicinal properties and socioeconomic importance, widely recognized since ancient Ayurvedic times. Despite i...
Azadirachta indica (A. indica) A. Juss., commonly known as Neem, is a valuable multipurpose tree with profound medicinal properties and socioeconomic importance, widely recognized since ancient Ayurvedic times. Despite its prominence, knowledge about its genetic diversity within the metropolitan area of Ahmedabad is limited. This study marks the first in-depth exploration of the genetic diversity and population structure of A. indica in Ahmedabad. The authenticity of the species was validated through DNA barcoding, and a Geographical Information System (GIS) was used to collect the samples. A total of 35 A. indica accessions were analyzed using five Inter Simple Sequence Repeat (ISSR) primers. Genetic diversity and population structure were evaluated using Inter Simple Sequence Repeat (ISSR) markers through polymorphism assessment, clustering, ordination, and Bayesian population structure analyses. ISSRs revealed a high level of polymorphism (75.66%), indicating substantial genetic variability among accessions. An analysis of genetic diversity indices revealed low to moderate diversity (Hs = 0.14, Ht = 0.217, I = 0.217). Analysis of Molecular Variance (AMOVA) analysis depicted 81% variation within the population and 19% among the population. Low to moderate genetic differentiation (Gst = 0.319) and moderate gene flow (Nm = 1.06) indicated that urban development has not hindered gene flow among populations. Mantel's test revealed a weak but significant correlation between genetic and geographic distances, suggesting limited isolation by distance. The estimated ΔK using STRUCTURE exhibited two subpopulations, representing two gene pools for A. indica accessions (K = 2). Collectively, these patterns indicate that urbanization has not severely disrupted genetic connectivity in A. indica, reflecting its resilience and adaptive potential in a metropolitan environment. These findings provide pivotal knowledge for further understanding the genetic diversity and population structure of A. indica in one of the fastest-growing cities in India, which can be utilized for new breeding programmes, sustainable development and future conservation strategies around the globe.
A Novel Serum miRNA Panel (miR-145, miR-34a, and miR-222) for Schwannoma Diagnosis.
Lashkarboloki M, Bapiri P, Boozarpour S … +4 more , Asghari A, Minaeian S, Ahmadi S, Jahanbakhshi A
Biochem Genet · 2026 Apr · PMID 41945284 · Publisher ↗
Schwannomas are the most prevalent benign tumors in peripheral nerve. Gene expression alterations are key factors in the formation of schwannomas. MiRNAs, as desirable biomarkers, are usually used for diagnosis or treatm...
Schwannomas are the most prevalent benign tumors in peripheral nerve. Gene expression alterations are key factors in the formation of schwannomas. MiRNAs, as desirable biomarkers, are usually used for diagnosis or treatment of tumors. The aim of this study is to investigate the diagnostic value of tissue-derived differentially expressed miRNAs in schwannoma serum samples and evaluated target genes involvement in biological pathways. In silico analysis of microarray datasets was used to evaluate the differential expression of miRNAs and mRNAs. MiRNA target genes were predicted using StarBase tools. For further exploration, DAVID tools were used to investigate Gene Ontology of Biological Process, Cellular Components and Molecular Functions of target genes. Lastly, RT-qPCR was performed to determine miRNA expression levels in serum samples from 20 patients and 20 healthy individuals. Bioinformatics results identified 149 miRNAs with differential expression and among them seven miRNAs selected for further study. In addition microarray data analysis identified 2475 differentially expressed mRNAs, of which 761 were located in miRNA target genes. Functional enrichment analysis showed that these target genes were involved in schwannoma related pathways such as P53 and VEGF. Our experimental results demonstrated that among candidate miRNAs, miR-145, miR-34a and miR-222 were downregulated in the vestibular schwannoma patients compared with normal subjects and they could distinguish schwannoma samples from normal ones with AUC > 70%. In this study, we report for the first time three serum miRNAs in schwannoma patients, which may not act as exclusive biomarkers but represent a potentially valuable component of a circulating diagnostic panel.
CRISPR/Cas9-Mediated Knockout of the NAD-Dependent Lactate Dehydrogenases for Altered Stereospecific Lactic Acid Production in Lacticaseibacillus paracasei NC4.
Chu NH, Le HD, Quach NT … +6 more , Pham TKL, Ho NA, Nguyen THH, Tran XK, Pham BN, Chu HH
Biochem Genet · 2026 Apr · PMID 41945283 · Publisher ↗
The optical purity of lactic acid is a critical parameter for producing high-performance polylactic acid (PLA). To investigate the genetic basis of stereospecific lactic acid biosynthesis, the present study aimed to func...
The optical purity of lactic acid is a critical parameter for producing high-performance polylactic acid (PLA). To investigate the genetic basis of stereospecific lactic acid biosynthesis, the present study aimed to functionally characterize the roles of ldh1 and ldh2 in Lacticaseibacillus paracasei NC4 through targeted gene disruption. A CRISPR/Cas9 nickase-based system was employed to construct three mutant strains (Δldh1, Δldh2, and Δldh1Δldh2). Fermentation experiments were conducted under identical conditions, and the concentrations of D- and L-lactic acid were quantified using HPLC. Three mutant strains, Δldh1, Δldh2, and Δldh1Δldh2, were successfully constructed from the wild-type NC4 using the CRISPR-Cas9 system. Compared with the wild-type NC4, which produced 89.31 ± 0.21 g/L L-lactic acid and 10.74 ± 0.19 g/L D-lactic acid, the Δldh1 mutant produced 76.31 ± 2.22 g/L L-lactic acid and 7.72 ± 0.36 g/L D-lactic acid, while the Δldh2 mutant yielded 81.73 ± 0.46 g/L L-lactic acid and ND (not detected) D-lactic acid. The Δldh1Δldh2 double mutant generated 75.57 ± 2.96 g/L L-lactic acid and ND (not detected) D-lactic acid. The Δldh1Δldh2 double mutant similarly exhibited no detectable D-lactic acid formation, supporting the role of ldh2 in D-lactate biosynthesis. These results indicate that targeted deletion of ldh genes significantly alters the stereospecificity of lactic acid biosynthesis. In particular, deletion of ldh2 was sufficient to eliminate detectable D-lactic acid formation, whereas deletion of ldh1 alone did not completely abolish D-lactate production. Overall, this study provides functional genetic insight into the roles of ldh1 and ldh2 in controlling lactic acid stereospecificity in L. paracasei NC4 and establishes a genetic basis for future metabolic and process-oriented optimization of optically pure lactic acid production.
The Role of MicroRNAs Implicated in the Regulation of PI3K/AKT and Focal Adhesion Signaling Pathways in Chronic Obstructive Pulmonary Disease.
Korytina G, Markelov V, Nasibullin T … +6 more , Timasheva Y, Akhmadishina L, Aznabaeva Y, Gibadullin I, Kochetova O, Zagidullin N
Biochem Genet · 2026 Apr · PMID 41945282 · Publisher ↗
Chronic Obstructive Pulmonary Disease (COPD) is a complex respiratory disorder characterized by chronic inflammation and irreversible airflow limitation, primarily resulting from long-term exposure to harmful particles o...
Chronic Obstructive Pulmonary Disease (COPD) is a complex respiratory disorder characterized by chronic inflammation and irreversible airflow limitation, primarily resulting from long-term exposure to harmful particles or gases, primarily from smoking. Dysregulation of microRNAs (miRNAs) contributes to COPD pathogenesis, influencing inflammation, airway and vascular remodeling, and oxidative stress responses. The study evaluated the expression of selected miRNAs involved in PI3K/AKT and focal adhesion pathways as potential COPD biomarkers. Lung tissue and peripheral blood mononuclear cells (PBMCs) were collected from COPD patients and healthy controls. RT-qPCR and TaqMan™ MicroRNA Assay (Thermo Fisher Scientific) were used to quantify expression levels of miR-218-5p, miR-126-3p, miR-200a-3p, miR-18a-5p, miR-29a-3p, miR-34a-5p, miR-155-5p, miR-141-3p, miR-15b-5p, miR-379-5p, miR-150-5p, miR-570-3p. Nine miRNAs were differentially expressed in PBMCs, and six in lung tissue of COPD patients, with four miRNAs (miR-18a-5p, miR-34a-5p, miR-126-3p, and miR-218-5p) altered in both. Multivariate models constructed using multiple regression demonstrated strong discrimination of COPD patients from controls, with AUC of 0.899 (combined assessment of miR-218-5p, miR-126-3p, miR-150-5p, and miR-29a-3p expression in PBMCs) and 0.965 (combined assessment of miR-218-5p, miR-141-3p, miR-379-5p, and miR-18a-5p expression in lung tissue). In silico pathway enrichment analysis linked the differentially expressed miRNAs to PI3K/AKT signaling, protein processing in the endoplasmic reticulum, focal adhesion, apoptosis, autophagy, and cellular senescence. The identified miRNAs are promising COPD biomarkers reflecting key pathogenic processes. Further validation in independent cohorts and functional studies are needed to confirm their clinical utility and to clarify their roles in disease progression.
Mapping the Molecular Evolution and Role of Wild Rice GLYIII Protein-Encoding Genes in Abiotic Stress Response.
Bhowal B, Hasija Y, Singla-Pareek SL
Biochem Genet · 2026 Apr · PMID 41931228 · Publisher ↗
To address the need for sustainable food production amid rapid global climate change, developing rice varieties that grow optimally even under harsh conditions is essential. An effective approach in this direction would...
To address the need for sustainable food production amid rapid global climate change, developing rice varieties that grow optimally even under harsh conditions is essential. An effective approach in this direction would be to harness the stress resilience traits of the crop wild relatives (CWRs) of rice. Among the various crucial stress-responsive genes, the Glyoxalase III (GLYIII) gene family is of utmost importance for its ability to detoxify the toxic glycolytic byproduct, methylglyoxal (MG), in a less energy-intensive, single-step process, as well as for its multifaceted cytoprotective role. In our study, a comprehensive genome-wide search across the Oryza genus revealed that GLYIII genes are conserved across wild rice genotypes. Their number has expanded during domestication, driven by gene duplications. Interestingly, only a few orthologous pairs showed positive selection, suggesting that the functions of most others need to be constrained and or conserved.We found that higher GLYIII activity, Total Antioxidant Capacity, endogenous glutathione (GSH) levels, and free radical scavenging activity contributes to the stress resilience of wild rices O. punctata, O. meridionalis, and O. nivara, in addition to other factors. , , . , . Our qRT-PCR analysis revealed differential expression of the OpGLYIII, OmGLYIII, and OnGLYIII genes across different developmental stages and in response to various abiotic stresses. Furthermore, we report that wild rice GLYIII proteins, specifically OpGLYIII-3, OmGLYIII-3, and OnGLYIII-5, exhibit high catalytic efficiency over a broad pH range and at higher temperatures under in vitro assay conditions. Overexpression of these proteins was found to impart substantial stress resilience to the transformed E. coli cells. These findings collectively suggest that GLYIII proteins constitute a key component of the abiotic stress response machinery in wild rice.
Fragaria Nubicola (A Wild Strawberry) from Azad Kashmir: Its Molecular Identification and Screening of Thaumatin-Like and Defensin Ec-Amp-D2-Like Proteins.
Awan AS, Shahid R, Mushtaq Z
Biochem Genet · 2026 Apr · PMID 41931227 · Publisher ↗
Fragaria nubicola, wild strawberry, is recognized for having diverse medicinal properties which include antimicrobial, anti-diabetic, anti-inflammatory, antioxidant and neuroprotective effects. In this study, molecular i...
Fragaria nubicola, wild strawberry, is recognized for having diverse medicinal properties which include antimicrobial, anti-diabetic, anti-inflammatory, antioxidant and neuroprotective effects. In this study, molecular identification of Fragaria nubicola collected from Azad Kashmir was done using universal primers of rbcL and matK genes. Phylogenetic analysis showed resemblance of the both, rbcL (OR453942) and matK genes (OR399558), mainly to Fragaria nubicola, Fragaria vesca and Fragaria ananassa. Additionally, antimicrobial peptide (AMP) genes, thaumatin-like protein (ThLP) and defensin Ec-AMP-D2-like protein (DefLP), were identified and computationally analyzed from the Fragaria nubicola for their structural and functional properties. Both AMP genes, ThLP (372 bp) encoding 109 amino acids peptide and DefLP (139 bp) encoding 46 amino acids peptide, were submitted to NCBI GenBank database with accession numbers of OR415848 and OR453943 respectively. Physiological analysis demonstrated structural and thermal stability of both AMPs. Antimicrobial prediction tool predicted their high antimicrobial potential and significant protein-binding potential (Boman index), ThLP (1.32 kcal/mol) and DefLP (1.9 kcal/mol). ThLP showed higher susceptibility to proteolysis as compared to DefLP. Molecular docking studies showed ThLP exhibiting a strong binding affinity with chitin synthase (docking score: -350.17) and DefLP demonstrating stable interactions with lipoteichoic acid synthase (-227.25) and lipopolysaccharide heptosyltransferase (-219.37). Such results would emphasize the potential of ThLP and DefLP as valuable antimicrobial agents and confirm further the pharmaceutical significance of Fragaria nubicola and its AMPs. Further experimental studies are now necessary for validation of bioactivity and optimization of their structural properties. Moreover, molecular identification of other Fragaria species might discover more medicinal compounds.
A Universal, Cost-Effective, and Efficient rRNA Depletion Method for Bacterial mRNA Enrichment.
Chauhan R, Patel H, Rawat S
Biochem Genet · 2026 Apr · PMID 41931226 · Publisher ↗
The abundance of rRNA in cells makes it difficult to enrich mRNAs, especially in prokaryotes, as it lacks a poly(A) tail. Numerous methods and kits have been developed to enrich mRNAs in prokaryotes, which are either org...
The abundance of rRNA in cells makes it difficult to enrich mRNAs, especially in prokaryotes, as it lacks a poly(A) tail. Numerous methods and kits have been developed to enrich mRNAs in prokaryotes, which are either organism-specific or have less enrichment efficiency apart from being costly. The current protocol aims to remove bacterial ribosomal RNA via the enzymatic digestion method. 23S rRNA, 16S rRNA and 5S rRNA were amplified from total RNA via reverse transcription, followed by digestion of RNA via RNase H and digestion of DNA via DNase I, which tends to enrich the total mRNA. The off-target digestion was evaluated and confirmed by reverse transcription followed by PCR, and the results were compared with the cDNA amplified products. The presence of rRNA and four genes was confirmed via RT‒qPCR, which revealed 99.99% removal of 23S rRNA and 16S rRNA and 92.84% removal of 5S rRNA. The enriched sample shows an increase in the copy number of mRNA genes of 92.88, 88.66, 85.67 and 84.50% for norA, mecA, fib and sarA, respectively. This method is not only cost-effective but also efficiently removes rRNA from the total RNA of any prokaryote and can remove any gene from the RNA pool via using the respective gene primers.
2,6-Diaminopurine Induces ACTN3 Premature Termination Codon Readthrough.
Harada N
Biochem Genet · 2026 Apr · PMID 41931225 · Publisher ↗
The ACTN3 gene encodes a sarcomeric α-actinin-3 protein, which forms an anti-parallel dimer and constitutes the Z-lines in human skeletal muscle fast-twitch fibers. In human ACTN3, a nonsense mutation that replaces a CGA...
The ACTN3 gene encodes a sarcomeric α-actinin-3 protein, which forms an anti-parallel dimer and constitutes the Z-lines in human skeletal muscle fast-twitch fibers. In human ACTN3, a nonsense mutation that replaces a CGA codon for the 577th arginine (R) residue with a TGA premature termination codon (PTC; specified as X) produces the R577X polymorphism. Since ACTN3 577X mRNA is targeted and degraded by a cellular nonsense-mediated mRNA decay (NMD) system, individuals with the homozygous ACTN3 577XX genotype do not express α-actinin-3 protein in the muscles, resulting in a decrease in speed-oriented athletic performance and muscle mass. The PTC has been a target for translational readthrough using aminoglycoside antibiotics, which enable the full-length α-actinin-3 protein to be produced from the ACTN3 577X gene. However, this effect requires a supraphysiological dose (mM levels) and supportive NMD inhibition. Using expression plasmids and HEK293 cultured cells, in this paper I show that 2,6-diaminopurine (DAP), a recently identified natural compound with translational readthrough activity, can produce a full-length α-actinin-3 protein from the ACTN3 577X gene even when used alone and at a relatively low concentration (µM levels). Most ACTN3 577X alleles likely contain three missense mutations (Q523R, R628C, and R776Q). Full-length α-actinin-3 proteins derived from the ACTN3 577X gene formed more homodimers than α-actinin-3 proteins derived from the ACTN3 577R gene. These results indicate that DAP-induced translational readthrough has the potential to restore function to the lost gene ACTN3 577X in humans.
A Combined Approach: Karyotyping and QF-PCR for Comprehensive Genetic Screening in Male Infertility.
Dubey P, Trivedi S, Singh NK … +7 more , Yadav AK, Ashish, Khanam N, Yadav J, Singh S, Chaurasiya S, Singh R
Biochem Genet · 2026 Apr · PMID 41931224 · Publisher ↗
Male infertility is a significant reproductive health concern, with genetic abnormalities such as chromosomal aberrations and Y-chromosome microdeletions contributing substantially to severe spermatogenic failure. This c...
Male infertility is a significant reproductive health concern, with genetic abnormalities such as chromosomal aberrations and Y-chromosome microdeletions contributing substantially to severe spermatogenic failure. This cross-sectional study evaluated the prevalence and spectrum of chromosomal abnormalities and Y-chromosome microdeletions in infertile males from Eastern Uttar Pradesh using conventional karyotyping and quantitative fluorescence polymerase chain reaction (QF-PCR). A total of 134 infertile males were enrolled. Semen analysis was performed according to the World Health Organization (WHO) 6th edition guidelines. Peripheral blood samples were subjected to karyotyping, followed by Y-chromosome microdeletion analysis using QF-PCR in individuals with normal karyotypes. Chromosomal abnormalities were identified in 23.1% of cases, with mosaic karyotypes accounting for approximately 18% of the total cohort. Mosaic Klinefelter syndrome (46,XY/47,XXY) was the predominant abnormality, observed in 14.2% of cases. Among men with normal karyotypes (n = 103), Y-chromosome microdeletions were detected in 29% using the AZF v2 kit, mainly involving the AZFb and AZFc regions. Extended STS marker analysis further identified additional deletions in 31% of initially negative cases, including partial AZFc and AZFa-associated deletions, thereby significantly improving the overall diagnostic yield. These findings highlight the importance of a combined cytogenetic and molecular approach for the genetic evaluation of male infertility. While karyotyping remains essential for detecting large chromosomal abnormalities, extended STS-based molecular screening enhances diagnostic yield, particularly in resource-limited clinical settings.
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